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Developed by 
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Supported by 
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Multi-Arm Polymer Conjugated Immmunotherapies
Developer(s)
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Nektar Therapeutics Originator
https://www.nektar.com/
United States Nektar Therapeutics (Nasdaq: NKTR) is a clinical-stage biopharmaceutical company headquartered in San Francisco, California. Founded in 1990, the company specializes in immunotherapy, utilizing proprietary PEGylation and polymer conjugate technology platforms to develop drug candidates for autoimmune disorders, chronic inflammation, and oncology. |
Sponsor(s)
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No sponsor indicated |
Partnerships
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Bristol-Myers Squibb (BMS) https://www.bms.com/gb |
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AstraZeneca https://www.astrazeneca.co.uk/ |
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UCB Pharma https://www.ucb.com/ |
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Amgen https://www.amgen.com/ |
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Baxalta https://www.takeda.com/en-gb/ |
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ONO PHARMACEUTICAL CO., LTD. https://www.ono-pharma.com/en |
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Ampersand Capital Partners https://ampersandcapital.com/ |
Technology information
Type of technology
Polymer-based particles
Administration route
Intratumoral, Intravenous
Development state and regulatory approval
Antineoplastic and immunomodulating agents
Phase II
Not approved yet
Description
This technology uses multi‑arm polymer conjugates of TLR7/8 agonists to activate local antitumor immunity while minimizing systemic toxicity. Delivered intratumorally, these conjugates stay in the tumor, enhance antigen presentation, and boost CD8⁺ T‑cell responses. The release of the TLR7/8 agonist from the polymer conjugate depends on the linkage‑containing spacer (Xₐ) connecting the polymer (POLY) to the drug. When combined with a long‑acting IL‑2Rβ‑biased agonist, they produce synergistic, systemic antitumor effects and strong abscopal responses.
Technology highlight
1. Core Scaffold (R) – Polyol / Polythiol / Polyamine Backbone (Eg: pentaerythritol, glycerol, trimethylolpropane, polyglycerols) 2. Linker Atom (Oxygen (O), Sulfur (S), Nitrogen (–NH–)) 3. Polymer Arms (Polyethylene glycol 2,000–150,000 Da) 4. Linkage‑Containing Spacer (Xᵣ) 5. API
Technology main components
The conjugated complex has 1. Core Scaffold (R) – Polyol / Polythiol / Polyamine Backbone (Eg: pentaerythritol, glycerol, trimethylolpropane, polyglycerols) 2. Linker Atom (Oxygen (O), Sulfur (S), Nitrogen (–NH–)) 3. Polymer Arms (Polyethylene glycol 2,000–150,000 Da) 4. Linkage‑Containing Spacer (Xᵣ) 5. API
Information on the raw materials sourcing, availability and anticipated price
Not provided
Delivery device(s)
No delivery device
APIs compatibility profile
API desired features
Water-insoluble molecules
Unit: mg/mL
Small molecules
(i) Antiviral agents (particularly HIV and chronic viral infections) Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Integrase strand transfer inhibitors (INSTIs), Protease inhibitors; (ii) Antibacterial agents (including TB and chronic bacterial infections) Rifamycins, Macrolides, Fluoroquinolones; (iii) Antifungal agents; (iv) Antiparasitic agents; (v) Anti-inflammatory and immunomodulatory drugs; (vi) Anticancer agents and (vii) CNS-active drugs (viii) TLR 7/8 agonists N-[4-(4-amino-2- ethyl-1H-imidazo[4,5c]quinolin-1-yl)butyl
Proteins
Rezpegaldesleukin and Bempegaldesleukin
Additional solubility data
Not provided
Additional stability data
Not provided
API loading: Maximum drug quantity to be loaded
75-90 wt%
API co-administration
1 single API :
LogP
Min: 1.5 Max: 6.5
Scale-up and manufacturing prospects
Scale-up prospects
Not provided
Tentative equipment list for manufacturing
1. Reaction Vessels/bioreactors 2. Magnetic stirrers 3. Heating plates / heating mantles 4. Cooling baths (20°C, 50°C, 60°C operations described) 5. Temperature controllers / thermometers 6. Hand‑swirling for dissolution 7. Nitrogen/argon inert atmosphere setups (implied by anhydrous conditions) 8. Filtration apparatus (frit funnels, Büchner funnels) 9. Vacuum filtration setups 10. High‑vacuum drying systems (overnight drying)
Manufacturing
To manufacture multi-arm conjugated complex, we need ISO cleanroom (class not explicited mentioned). Step1: Derive polymer from Lactide, Glycolide, Caprolactone or Combinations thereof (copolymers) Step 2: Ring-opening polymerization - initiated by alcohol-based initiators, using metal-based catalysts (e.g., tin-based catalysts) Step 3: Polymer purification, Removal of unreacted monomer, Drying of the polymer prior to formulation use Step 4: API and Polymer complex formation using Melt or semi-solid processing or solvent based mixing.
Specific analytical instrument required for characterization of formulation
1. 500 MHz Bruker ¹H NMR spectrometer Drug content & release: 2. HPLC or UPLC 3. UV–Vis spectroscopy Polymer–drug interaction: 4. DSC (thermal behavior) 5. FTIR (compatibility assessment) Physical characterization: 6. Particle size analyzers (if particulate) 7. Microscopy (optical / SEM implied) Stability & performance: 8. Dissolution or release testing apparatus 9. Accelerated stability chambers
Clinical trials
REZOLVE-AD
Identifier
NCT06136741
Link
https://clinicaltrials.gov/study/NCT06136741
Phase
Phase II
Status
Not provided
Sponsor
Nektar Therapeutics
More details
This is an interventional, randomized, parallel group, treatment, Phase IIb, double blind, 4-arm study to assess the effect of pegylated-recombinant-human interleukin-2 (rezpegaldesleukin) in adult participants with moderate to severe atopic dermatitis. The estimated duration is 15-35 days for screening, an Induction Period of 16 weeks, a Maintenance Period from Week 16-Week 52, and a Posttreatment Follow-Up Period for an additional year up to approximately Week 104 for all patients. Patients with a response at Week 16 (end of induction therapy) will be re-randomized for the maintenance therapy period.
Purpose
A Phase 2b Study to Evaluate Rezpegaldesleukin (Rezpeg) in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2023-11-15
Anticipated Date of Last Follow-up
2026-01-16
Estimated Primary Completion Date
Not provided
Estimated Completion Date
2026-12-31
Actual Primary Completion Date
2025-05-06
Actual Completion Date
Not provided
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Adults (from at least 18 years of age) with AD as defined by the American Academy of Dermatology Consensus Criteria for 1 year or longer prior to screening. * AD disease severity at screening and randomization: * EASI of 16 or higher * IGA of 3 or 4 * BSA of 10% or more * Documented history, within 6 months prior to the screening visit, of either inadequate response or inadvisability of topical treatments. * Able to complete patient questionnaires. * Able and willing to comply with requested study visits and procedures. * Able and willing to provide written informed consent. Exclusion Criteria: * Prior use of systemic immune modulating therapies for AD (i.e., JAK inhibitors or biologics) * Other skin conditions that would interfere with assessment of AD * Tr
Health status
Study type
Interventional (clinical trial)
Enrollment
396
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Quadruple-blind masking
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
23-358-06
Identifier
NCT06340360
Link
https://clinicaltrials.gov/study/NCT06340360
Phase
Phase II
Status
Not provided
Sponsor
Nektar Therapeutics
More details
This is an interventional, randomized, double blind, parallel group, placebo-controlled, Phase 2b, 3-arm study to assess the effect of pegylated-recombinant-human interleukin-2 (rezpegaldesleukin) in adult participants with severe to very severe alopecia areata. The estimated duration includes a screening period of up to 35 days, a 36-week treatment period, an optional 16-week treatment extension period, and a 24-week follow-up period. The maximum study duration is approximately 81 weeks for all participants.
Purpose
A Phase 2b Study to Evaluate Rezpegaldesleukin (Rezpeg) in the Treatment of Severe to Very Severe Alopecia Areata in Adult Patients (Rezolve AA)
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2024-04-02
Anticipated Date of Last Follow-up
2025-12-24
Estimated Primary Completion Date
Not provided
Estimated Completion Date
2026-08-01
Actual Primary Completion Date
2025-11-26
Actual Completion Date
Not provided
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Adults who are at least 18 years and ≤60 years for males (≤70 years of age for females) old at the time of informed consent * Diagnosis of Alopecia Areata (AA) severity at screening and baseline: 1. severe to very severe AA (≥ 50% scalp involvement) as measured using the SALT score 2. Documented history over 6 months with no spontaneous improvement prior to baseline 3. Current episode of severe to very severe AA of less than 8 years * Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and baseline. * While on investigational product and for at least 30 days after taking the last dose of investigational product (IP), WOCBP who engage in activity in which conception is possible must use approved highly effective contraceptiv
Health status
Study type
Interventional (clinical trial)
Enrollment
94
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Quadruple-blind masking
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
12-181-04
Identifier
NCT01619839
Link
https://clinicaltrials.gov/study/NCT01619839
Phase
Phase II
Status
Completed
Sponsor
Nektar Therapeutics
More details
NKTR-181 is being developed as an analgesic compound for the treatment of moderate to severe chronic pain - active as a mu agonist, but with inherent molecular properties designed to provide a unique clinical profile, including most notably, reduced CNS side effects and an attenuated attractiveness as a target of abuse.
Purpose
A Phase 2 Study To Assess The Efficacy, Tolerability, And Safety OF NKTR-181 In Subjects With Chronic OA Knee Pain
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2012-06-01
Anticipated Date of Last Follow-up
2021-07-09
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2013-08-01
Actual Completion Date
2013-09-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Willing and able to give written informed consent; * Willing and able to understand the study procedures, and comply with all study procedures; * Females or males, age ≥ 18 years old; * Body mass index 18-39, inclusive; * In good general health; * Clinical diagnosis of OA in one or both knees; * Have been on a stable regimen of pain medication for the management of OA knee pain; * Not experiencing adequate pain relief with their current dosing regimen; * Women of childbearing potential (WCBP) must agree to use highly effective methods of birth control. Male subjects must agree to use contraception. Exclusion Criteria: * Females who are pregnant or lactating; * Known history of hypersensitivity, intolerance, or allergy to opioids; * Diagnosed as having any chronic p
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
296
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Quadruple-blind masking
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
11-PIR-09
Identifier
NCT01457118
Link
https://clinicaltrials.gov/study/NCT01457118
Phase
Phase II
Status
Completed
Sponsor
Nektar Therapeutics
More details
The study objective of this open label, multicenter study is to provide access to NKTR-102 treatment to subjects previously enrolled in a NKTR-102 study who are without signs of disease progression since receiving NKTR-102. In addition the study will evaluate the safety of continued exposure to NKTR-102, observe disease status and survival status in subjects receiving NKTR-102, and evaluate the efficacy of NKTR-102 in subjects with advanced or metastatic solid tumors.
Purpose
An Extension Study of NKTR-102 in Cancer Patients Previously Enrolled in NKTR-102 Studies
Interventions
Intervention 1
Intervention 2
Intervention 3
Intervention 4
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2011-10-01
Anticipated Date of Last Follow-up
2021-07-09
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2017-08-01
Actual Completion Date
2017-11-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion: 1. Received prior treatment with NKTR-102 2. Free of disease progression since receiving NKTR-102 3. Adequate bone marrow and organ function 4. Treatment with NKTR-102 in the extension study to begin within 8 weeks after receipt of their of last dose of NKTR-102 5. Agree to use adequate contraception Exclusion: 1. Treatment with other anti-cancer therapy between the last dose of NKTR-102 in the prior study and before first dose of NKTR-102 in the extension study 2. A toxicity that requires a 3rd dose reduction after taking NKTR-102 or are scheduled to receive a dose \< 70 mg/m2 upon entry into this study 3. Pregnancy or lactation
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
27
Allocation
Not provided
Intervention model
Single group assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
BEACON
Identifier
NCT01492101
Link
https://clinicaltrials.gov/study/NCT01492101
Phase
Phase III
Status
Completed
Sponsor
Nektar Therapeutics
More details
The study is designed as an open-label, randomized, parallel, two arm, multicenter, international Phase 3 study in patients with recurrent or metastatic breast cancer previously treated with cytotoxic chemotherapy regimens. The primary study objective is to compare overall survival of patients who receive NKTR-102 given once every 21 days to patients who receive treatment of Physician's Choice selected from a list of seven single-agent intravenous therapies.
Purpose
The BEACON Study (Breast Cancer Outcomes With NKTR-102)
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2011-12-01
Anticipated Date of Last Follow-up
2021-05-06
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2016-04-01
Actual Completion Date
2016-06-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- Female
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria (major highlights): * Patient is an adult female with histologically or cytologically confirmed carcinoma of the breast for whom single-agent cytotoxic chemotherapy is indicated * Patient can have either measurable or non-measurable disease by RECIST. * Patient has received prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic setting) with an anthracycline, a taxane and capecitabine * Patient has minimum of 2 and a maximum of 5 prior cytotoxic chemotherapy regimens with the last dose administered within 6 months. A minimum of two chemotherapy regimens had to be for locally recurrent and/or metastatic disease. All therapy received prior to a diagnosis of metastatic disease (eg, neoadjuvant, adjuvant or repeated adjuvant therapy following a second re
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
852
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
08-PIR-04
Identifier
NCT00806156
Link
https://clinicaltrials.gov/study/NCT00806156
Phase
Phase II
Status
Completed
Sponsor
Nektar Therapeutics
More details
This is a multicenter, open-label, two-arm, 2-stage, Phase 2 study of NKTR-102 in patients with metastatic or locally advanced platinum-resistant ovarian cancer. Approximately 70 patients will be randomized 1:1 into one of two treatment arms. NKTR-102 will be administered at a dose level of 145 mg/m\^2 in both arms. In Arm A, NKTR-102 will be given on a q14d schedule. In Arm B, NKTR-102 will be given on a q21d schedule. After the initial 70 patients have been enrolled, Arm B will enroll approximately 110 additional patients.
Purpose
Study to Evaluate the Safety and Efficacy of NKTR-102 in Patients With Metastatic or Locally Advanced Ovarian Cancer
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2008-10-01
Anticipated Date of Last Follow-up
2021-07-09
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2012-10-01
Actual Completion Date
2013-01-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- Female
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer 2. Inoperable metastatic or locally advanced ovarian cancer 3. Platinum-resistant ovarian cancer defined as progression by RECIST within 6 months of last dose of most recent platinum drug 4. Platinum-resistant patients who have progressed after receiving PLD (Doxil/Caelyx)therapy in a platinum-resistant setting or who otherwise unable to receive PLD therapy. 5. Diseases must be measurable as defined by RECIST in at least 1 lesion not previously irradiated. 6. ECOG performance score of 0 or 1. 7. Adequate organ and bone marrow functions at Screening. Exclusion Criteria: 1. Patients who have had chemotherapy or radiotherapy within 4 we
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
178
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
08-PIR-03
Identifier
NCT00856375
Link
https://clinicaltrials.gov/study/NCT00856375
Phase
Phase II
Status
Completed
Sponsor
Nektar Therapeutics
More details
This study will evaluate whether NKTR-102, an investigational drug has an anti-tumor effect in patients with colorectal cancer. This study will also evaluate how the safety and anti-tumor activity of NKTR-102 compares with irinotecan, a cancer drug that is approved for use in the US for treatment of patients with certain types of colorectal cancer.
Purpose
NKTR-102 Versus Irinotecan in Patients With Second-Line, Irinotecan-Naïve, KRAS Mutant, Colorectal Cancer
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2008-12-01
Anticipated Date of Last Follow-up
2021-07-09
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2014-07-01
Actual Completion Date
2014-12-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * metastatic colorectal cancer * tumor with k-ras mutation Exclusion Criteria: * More than 1 prior regimen for treatment of metastatic disease
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
83
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
08-PIR-05
Identifier
NCT00802945
Link
https://clinicaltrials.gov/study/NCT00802945
Phase
Phase II
Status
Completed
Sponsor
Nektar Therapeutics
More details
This is a multicenter, open-label, two-arm, 2-stage, Phase 2 study of NKTR-102 in patients with metastatic or locally advanced breast cancer whose disease has failed prior taxane-based treatment in the metastatic setting. Patients will be randomized 1:1 into one of two treatment arms. NKTR 102 will be administered at a dose level of 145 mg/m2 in both arms. In Arm A, NKTR-102 will be given on a q14d schedule. In Arm B, NKTR-102 will be given on a q21d schedule. Approximately 70 patients may be evaluated in this study with approximately 35 patients enrolled in each treatment arm.
Purpose
Study to Evaluate the Safety and Efficacy of NKTR-102 in Patients With Metastatic or Locally Advanced Breast Cancer
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2008-10-01
Anticipated Date of Last Follow-up
2018-06-07
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2011-10-01
Actual Completion Date
2012-01-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: 1. Inoperable metastatic or locally advanced breast cancer 2. No more than 2 prior chemotherapy regimens given in a metastatic or locally advanced setting and prior treatment in the metastatic setting must have included a taxane Exclusion Criteria: 1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Day 1 of Cycle 1 2. Patients who have had any major surgery within 4 weeks prior to Day 1 of Cycle or minor surgery within 2 weeks prior to Day 1 of Cycle 1
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
70
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
07-PIR-02
Identifier
NCT00598975
Link
https://clinicaltrials.gov/study/NCT00598975
Phase
Phase II
Status
Completed
Sponsor
Nektar Therapeutics
More details
Study 07-PIR-02 is a Phase 2 study designed to evaluate the safety and efficacy of NKTR-102 (PEG-irinotecan) for the treatment of patients with colorectal cancer (CRC). The study is comprised of two sequential components - Phase 2a and Phase 2b. The Phase 2a portion is an open-label, dose-finding trial in multiple solid tumor types that are refractory to standard curative or palliative therapies. The primary endpoint of the Phase 2a is to establish the /recommended Phase 2 Dose (RPTD) of NKTR-102 by measuring the frequency of Dose Limiting Toxicity (DLT). The Phase 2b portion is an open-label, randomized, two-arm study in patients with second-line metastatic colorectal cancer and study participants will be randomized (1:1) to receive either NKTR-102 and cetuximab or irinotecan and cetuxima
Purpose
NKTR-102 in Combination With Cetuximab in Patients With Refractory Solid Tumors (Phase 2a) and Metastatic or Locally Advanced Colorectal Cancer (Phase 2b)
Interventions
Intervention 1
Intervention 2
Intervention 3
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2008-02-01
Anticipated Date of Last Follow-up
2021-07-09
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2009-05-01
Actual Completion Date
2011-12-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Male and non-pregnant, non-lactating female patients with an ECOG performance score \<3 who have any type of solid tumor refractory to standard therapy and who have adequate bone marrow and organ function at screening. Exclusion Criteria: * Patients must not have used any CYP3A4 inducers or inhibitors with 2 weeks prior to the first day of study drug treatment.
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
18
Allocation
Not provided
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
17604
Identifier
NCT04998487
Link
https://clinicaltrials.gov/study/NCT04998487
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to estimate how much LY3471851 gets into the blood stream and how long it takes the body to remove it when administered under the skin in healthy participants. The study will also evaluate the safety and tolerability of LY3471851. The study is expected to last up to 87 days for each participant.
Purpose
A Single-Dose Study of LY3471851 in Healthy Participants
Interventions
Intervention 1
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2021-08-16
Anticipated Date of Last Follow-up
2023-11-15
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2022-07-06
Actual Completion Date
2022-07-06
Studied populations
Age Cohort
- Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied populations
Inclusion Criteria: * Overtly healthy males or females, as determined by medical history and physical examination. * Body weight greater than 55 kilograms (kg) and body mass index (BMI) within the range of 19 to 30 kilograms per meter squared (kg/m²) Exclusion Criteria: * Have evidence of clinically significant active infection, including fever 100.5ºF (38ºC) or above, within 28 days of dosing or Day 1 (before dosing) * Have had serious, opportunistic, or chronic/recurring infection within 6 months prior to screening. Examples include but are not limited to infections requiring intravenous antibiotics, hospitalization, or prolonged treatment * Are immunocompromised per investigator judgment.
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
71
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
18-214-12
Identifier
NCT04955262
Link
https://clinicaltrials.gov/study/NCT04955262
Phase
Phase I
Status
Withdrawn
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to investigate the utility of the new investigational imaging agent ⁸⁹Zr Df-IAB22M2C (CD8 PET/CT tracer) to monitor CD8 T-cell expansion and trafficking within tumors and associated tissues in patients with metastatic melanoma undergoing treatment with bempegaldesleukin and nivolumab as a single agent and in combination.
Purpose
A CD8 Positron Emission Tomography With Computed Tomography (PET/CT) Study Using ⁸⁹Zr Df-IAB22M2C in Patients With Metastatic Melanoma Receiving Bempegaldesleukin (NKTR-214) and Nivolumab
Interventions
Intervention 1
Intervention 2
Intervention 3
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
2019-08-01
Actual Start Date
Not provided
Anticipated Date of Last Follow-up
2021-06-28
Estimated Primary Completion Date
2021-06-01
Estimated Completion Date
2022-01-01
Actual Primary Completion Date
Not provided
Actual Completion Date
Not provided
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Key Inclusion Criteria: * Provide written, informed consent to participate in the study and follow the study procedures * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 * Measurable disease per RECIST 1.1 criteria * Patients must have histologically confirmed metastatic melanoma with measurable, stage IV disease per American Joint Committee on Cancer (AJCC) staging system * In patients with a single RECIST measurable lesion, the lesion must be a non-cutaneous lesion. * Fresh biopsy * Treatment-naive patients (i.e., no prior systemic anticancer therapy for unresectable or metastatic melanoma). Key Exclusion Criteria: * Patients who have an active, known or suspected autoimmune disease * Patients must not have received prior IL-2 therapy * Prior treatment with an anti
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
Not provided
Allocation
Not provided
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
18-255-01
Identifier
NCT05664217
Link
https://clinicaltrials.gov/study/NCT05664217
Phase
Phase II/III
Status
Terminated
Sponsor
Nektar Therapeutics
More details
This study will evaluate the safety and efficacy of NKTR-255 following CD19-directed chimeric antigen (CAR)-T cell therapy in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). NKTR-255 is an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer. T cells are infection fighting blood cells that can kill tumor cells. Chimeric antigen (CAR)-T cell product consists of genetically engineered T-cells, modified to recognize CD19, a protein on the surface of cancer cells. These CD19-specific T cells may help the body's immune system identify and kill CD19-positive cancer cells. Giving NKTR-255 following the treatment with CD19 CAR-T cell therapy may work better in treating large B-cell lymphoma than either drug alone.
Purpose
NKTR-255 vs Placebo Following CD19-directed CAR-T Therapy in Patients With Relapsed/Refractory Large B-cell Lymphoma
Interventions
Intervention 1
Intervention 2
Intervention 3
Intervention 4
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2022-12-23
Anticipated Date of Last Follow-up
2025-02-11
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2024-05-22
Actual Completion Date
2024-08-16
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Key Inclusion Criteria: 1. Male or female ≥ 18 years of age at the time of consent. 2. Received standard of care therapy with axi-cel or liso-cel (Stage 1 and Stage 2), or tisa-cel (Stage 2 only), for the respective FDA (or Summary of Product Characteristics \[SmPC\]) approved indication(s): 1. liso-cel: Patients with LBCL (including diffuse LBCL \[DLBCL\] not otherwise specified \[including DLBCL arising from indolent lymphoma\], high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma Grade 3B), who have: 1. refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; 2. refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hema
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
15
Allocation
Randomized
Intervention model
Sequential assignment
Intervention model description
Not provided
Masking
Quadruple-blind masking
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
18-255-01
Identifier
NCT05664217
Link
https://clinicaltrials.gov/study/NCT05664217
Phase
Phase II/III
Status
Terminated
Sponsor
Nektar Therapeutics
More details
This study will evaluate the safety and efficacy of NKTR-255 following CD19-directed chimeric antigen (CAR)-T cell therapy in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). NKTR-255 is an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer. T cells are infection fighting blood cells that can kill tumor cells. Chimeric antigen (CAR)-T cell product consists of genetically engineered T-cells, modified to recognize CD19, a protein on the surface of cancer cells. These CD19-specific T cells may help the body's immune system identify and kill CD19-positive cancer cells. Giving NKTR-255 following the treatment with CD19 CAR-T cell therapy may work better in treating large B-cell lymphoma than either drug alone.
Purpose
NKTR-255 vs Placebo Following CD19-directed CAR-T Therapy in Patients With Relapsed/Refractory Large B-cell Lymphoma
Interventions
Intervention 1
Intervention 2
Intervention 3
Intervention 4
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2022-12-23
Anticipated Date of Last Follow-up
2025-02-11
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2024-05-22
Actual Completion Date
2024-08-16
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Key Inclusion Criteria: 1. Male or female ≥ 18 years of age at the time of consent. 2. Received standard of care therapy with axi-cel or liso-cel (Stage 1 and Stage 2), or tisa-cel (Stage 2 only), for the respective FDA (or Summary of Product Characteristics \[SmPC\]) approved indication(s): 1. liso-cel: Patients with LBCL (including diffuse LBCL \[DLBCL\] not otherwise specified \[including DLBCL arising from indolent lymphoma\], high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma Grade 3B), who have: 1. refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; 2. refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hema
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
15
Allocation
Randomized
Intervention model
Sequential assignment
Intervention model description
Not provided
Masking
Quadruple-blind masking
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
17414
Identifier
NCT04133116
Link
https://clinicaltrials.gov/study/NCT04133116
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to explore the safety and tolerability of LY3471851 in healthy Japanese and Caucasian participants. The study will also estimate how much LY3471851 gets into the blood stream and how long it takes the body to remove it. The study is expected to last about 7 weeks for each participant.
Purpose
A Study of LY3471851 in Healthy Participants
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2019-10-29
Anticipated Date of Last Follow-up
2023-11-15
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2020-03-06
Actual Completion Date
2020-03-06
Studied populations
Age Cohort
- Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied populations
Inclusion Criteria: * Are healthy males or females, as determined by medical history and physical examination * Are first generation Japanese or are Caucasian * Have a body mass index (BMI) of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive, at the time of screening Exclusion Criteria: * Are currently enrolled in a clinical study involving an investigational product (IP) or any other type of medical research judged not to be scientifically or medically compatible with this study * Have an abnormal blood pressure and/or pulse rate as determined by the investigator * Regularly use known drugs of abuse and/or show positive findings on drug screening * Are immunocompromised per investigator judgment
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
36
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
18-181-26
Identifier
NCT03802227
Link
https://clinicaltrials.gov/study/NCT03802227
Phase
Phase I
Status
Terminated
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to evaluate the effect of NKTR-181 on brain activity in healthy, non-physically dependent recreational opioid users. This study will last about 88 days for each participant.
Purpose
A Study Using fMRI Imaging to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users.
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2018-10-22
Anticipated Date of Last Follow-up
2021-07-06
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2019-12-17
Actual Completion Date
2020-01-03
Studied populations
Age Cohort
- Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied populations
Key Inclusion Criteria: * Healthy male and female recreational opioid users, 18-65 years of age inclusive. * Body Mass Index (BMI) between 19.0 to 45.0kg/m2 * Have at least one urine drug screen positive for opioids during Screening to confirm recreational opioid use. Subjects testing positive for methadone or buprenorphine prescribed for treatment will be excluded. * Subjects must agree to practice adequate contraception as outlined in the protocol. Key Exclusion Criteria: * Any metal fragments or other bodily metal that would pose a risk to subjects during MRI scanning as determined by the MRI technologist and/or MRI physicist * Any clinically significant disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, central nervous
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
8
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Triple-blind masking
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Not provided
Studied route(s) of administration
Not provided
Use case
Treatment
Key resources
20-214-34
Identifier
NCT04646044
Link
https://clinicaltrials.gov/study/NCT04646044
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The main purpose of this phase-1b, multicenter, randomized double-blind, placebo-controlled, trial is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of bempegaldesleukin (BEMPEG; NKTR-214) in combination with standard of care (SOC) in adult patients with mild COVID-19 (coronavirus disease 2019). The trial will also define the recommended phase 2 dose (RP2D) of bempegaldesleukin in patients with mild COVID-19.
Purpose
A Placebo Controlled Trial of Bempegaldesleukin (BEMPEG; NKTR-214) With Standard of Care in Patients With Mild COVID-19
Interventions
Intervention 1
Intervention 2
Intervention 3
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2020-11-13
Anticipated Date of Last Follow-up
2024-03-05
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2021-05-11
Actual Completion Date
2021-05-18
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Male or female patients, age 18 years or older on the day of signing the informed consent form. * Agrees to admission to an in-patient facility for monitoring from Days 1 to 8, inclusive. * Symptoms of mild illness with COVID-19 without shortness of breath, dyspnea, or clinical signs indicative of more serious COVID-19. * Laboratory confirmed SARS-CoV-2 infection within 4 days prior to the screening visit or during the 7-day screening period. * Respiratory rate \< 20 breaths per minute, heart rate \< 90 beats per minute (bpm). * Oxygen saturation by pulse oximetry \> 93% on room air. * Body mass index \< 35 kg/m2. * Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min. * Alanine transaminase (ALT) or aspartate transaminase (AST) \< 2 x upper limit of normal (ULN)
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
30
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
17237
Identifier
NCT04380324
Link
https://clinicaltrials.gov/study/NCT04380324
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to evaluate the safety and tolerability of a study drug known as LY3471851 in healthy participants. The study will last about 50 days for each participant.
Purpose
A Study of NKTR-358 (LY3471851) in Healthy Participants
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2017-03-19
Anticipated Date of Last Follow-up
2023-11-15
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2019-01-20
Actual Completion Date
2019-01-20
Studied populations
Age Cohort
- Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied populations
Inclusion Criteria: * Overtly healthy males and females, as determined by medical history and physical examination * Have a body mass index (BMI) of 18.0 to 32.0 kilograms per square meter (kg/m²) Exclusion Criteria: * Previous or current autoimmune disease/disorder * Current active bacterial, viral, or fungal infection * Administration of an inactivated vaccine within two weeks of study drug administration or live attenuated vaccine within 90 days of dosing .
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
100
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
20-214-36
Identifier
NCT04969861
Link
https://clinicaltrials.gov/study/NCT04969861
Phase
Phase II/III
Status
Terminated
Sponsor
Nektar Therapeutics
More details
This is a multicenter, randomized, open-label, Phase 2/3 study that will evaluate the efficacy and safety of bempegaldesleukin (BEMPEG; NKTR-214) combined with pembrolizumab compared with pembrolizumab monotherapy in patients with recurrent or metastatic HNSCC with positive PD-L1 expression (CPS ≥ 1).
Purpose
BEMPEG With Pembrolizumab vs Pembrolizumab Alone in Patients With Metastatic or Recurrent HNSCC (PROPEL-36)
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2022-03-09
Anticipated Date of Last Follow-up
2022-12-16
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2022-04-22
Actual Completion Date
2022-04-22
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Provide written, informed consent to participate in the study and follow the study procedures. * Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF). * Have histologically or cytologically-confirmed recurrent or metastatic HNSCC that is considered incurable by local therapies. * No prior systemic therapy for recurrent or metastatic disease. * The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. * Patients may not have a primary tumor site of nasopharynx (any histology) and/or unknown primary. * Have measurable disease based on RECIST 1.1 as determined by the local site Investigator. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Measure Descripti
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
1
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
19-255-03
Identifier
NCT04616196
Link
https://clinicaltrials.gov/study/NCT04616196
Phase
Phase I/II
Status
Completed
Sponsor
Nektar Therapeutics
More details
This is a Phase 1b/2, open-label multicenter study evaluating NKTR-255 as a monotherapy and together with cetuximab in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal carcinoma (CRC).
Purpose
Study of NKTR 255 in Combination With Cetuximab in Solid Tumors
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2020-10-30
Anticipated Date of Last Follow-up
2025-05-26
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2023-03-30
Actual Completion Date
2023-03-30
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Key Inclusion Criteria: * Histologically confirmed diagnosis of a locally advanced or metastatic HNSCC or CRC. * Life expectancy \> 12 weeks as determined by the Investigator. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Measurable disease per RECIST 1.1. HNSCC: * Progression on any first or second line platinum-based chemotherapy and/or anti-PD-1 or programmed death-ligand 1 antibody. CRC: * Patients must have received or were intolerant to at least 2 prior cancer therapy regimens administered for metastatic disease. Key Exclusion Criteria: * Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug(s) * Prior surgery or radiotherapy within 14 days of initiating study drug(s) * Evidence
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
25
Allocation
Not provided
Intervention model
Sequential assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
18-255-02
Identifier
NCT04136756
Link
https://clinicaltrials.gov/study/NCT04136756
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
Patients will receive intravenous (IV) NKTR-255 in 21 or 28 day treatment cycles. During the Part 1 dose escalation portion of the trial, patients will either receive NKTR-255 as monotherapy, NKTR-255 administered as a doublet with daratumumab subcutaneous (DARZALEX FASPRO TM), or NKTR-255 administered as a doublet with rituximab. After determination of the recommended Phase 2 dose (RP2D) of NKTR-255, NKTR-255 will be evaluated in Part 2. During the Part 2 dose expansion portion of the trial, patients will either receive NKTR-255 as monotherapy, NKTR-255 administered as a doublet with daratumumab subcutaneous (DARZALEX FASPRO TM), or NKTR-255 administered as a doublet with rituximab. This is a Phase 1 study to evaluate safety and tolerability of NKTR-255 alone and in combination with dara
Purpose
NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma
Interventions
Intervention 1
Intervention 2
Intervention 3
Intervention 4
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2019-10-07
Anticipated Date of Last Follow-up
2023-06-13
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2023-04-24
Actual Completion Date
2023-04-24
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Key Inclusion Criteria: * Patients must have relapsed or refractory MM or NHL with no available therapies that would confer clinical benefit for their primary disease. * For MM patients, measurable relapsed or refractory MM as defined by the IMWG Criteria (Kumar, 2016) following treatment with at least 3 lines of therapy with no other available treatment that would confer benefit. * For NHL patients, measurable or detectable disease according to International Myeloma Working Group (IMWG) and the Lugano Classification. Extranodal NHL disease that is measurable by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging only is allowed. * Estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m2. * Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2 Patien
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
30
Allocation
Not provided
Intervention model
Sequential assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
12-102-13
Identifier
NCT01991678
Link
https://clinicaltrials.gov/study/NCT01991678
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The purpose of this study is to investigate the PK and safety of NKTR-102 in patients with mild, moderate, or severe hepatic impairment.
Purpose
A Study in Cancer Patients With Hepatic Impairment to Evaluate the Pharmacokinetics and Safety of NKTR-102 (Etirinotecan Pegol)
Interventions
Intervention 1
Intervention 2
Intervention 3
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2013-11-01
Anticipated Date of Last Follow-up
2017-10-05
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2017-05-01
Actual Completion Date
2017-09-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Relapsed or progressive advanced solid tumor malignancies * Measurable or non-measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Life expectancy greater than 3 months * Resolution of all acute toxic effects of prior chemotherapy, and other cancer treatments * Adequate bone morrow and kidney function * No signs of decompensated liver cirrhosis or ascites requiring therapeutic paracentesis * Agree to use adequate contraception Exclusion Criteria: * Previous chemotherapy, immunotherapy, chemo-embolization, targeted therapy or investigational agent for malignancy within 4 weeks prior to day 1 * Cytochrome P450 CYP3A4 inducers and inhibitors within 4 weeks prior to day 1 * Intake of grapefruit, grapefruit juice, Seville oranges, o
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
25
Allocation
Not provided
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
12-102-12
Identifier
NCT01976143
Link
https://clinicaltrials.gov/study/NCT01976143
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The purpose of this research study is to evaluate the effect of NKTR-102 on the QT/QTc interval in patients with advanced or metastatic solid tumors
Purpose
A Study in Cancer Patients to Evaluate the Effect of a Single Dose of NKTR-102 (Etirinotecan Pegol) on the QTc Interval and to Assess Pharmacokinetics and Safety
Interventions
Intervention 1
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2014-02-01
Anticipated Date of Last Follow-up
2016-12-20
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2016-06-01
Actual Completion Date
2016-09-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Advanced or metastatic solid tumor refractory to standard therapy * Measurable or non-measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Resolution of acute toxic effects of prior chemotherapy and other cancer treatments * Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram * Adequate bone morrow and organ function * Electrolytes within normal limits * Stopped tobacco use for 4 weeks prior to day 1 and during the study * Agree to use adequate contraception Exclusion Criteria: * Previous anti-cancer therapy for malignancy within 4 weeks (6 weeks for the nitrosoureas or mitomycin C) before day 1 * Treatment with antiarrythmic drugs and any medication known to cause QTc prolongation within 4 weeks before screenin
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
33
Allocation
Not provided
Intervention model
Single group assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
17603
Identifier
NCT05565729
Link
https://clinicaltrials.gov/study/NCT05565729
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The purpose of this study is to compare two different formulations (test \& reference) of LY3471851 in healthy participants. This study will compare how much of each formulation gets into the blood stream and how long it takes the body to remove it. Information about any side effects that may occur will also be collected. Participants will remain in the study for about 12 weeks, after receiving the study drug that is LY3471851.
Purpose
A Phase I Study of LY3471851 in Healthy Participants
Interventions
Intervention 1
Intervention 2
Intervention 3
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2022-10-05
Anticipated Date of Last Follow-up
2023-11-15
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2023-02-23
Actual Completion Date
2023-02-23
Studied populations
Age Cohort
- Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
Yes
Comments about the studied populations
Inclusion Criteria: * Participants who are overtly healthy as determined by medical history and physical examination * Have body weight greater than 45 kilograms (kg) and body mass index within the range 18.0 to 32.0 kilograms per square meter (kg/m²) * Male and female participants must agree to adhere to contraceptive requirements Exclusion Criteria: * Have an abnormality in the 12-lead electrocardiogram (ECG), vital signs, or both * Have had symptomatic herpes zoster within 3 months prior to screening * Have a known allergy or hypersensitivity to levocetirizine * Intend to use prescription or nonprescription medication within 14 days or 5 half-lives prior to dosing * Have received treatment with biologic agents within 3 months or 5 half-lives prior to dosing * Smoke more than 10 cigar
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
41
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
PROPEL
Identifier
NCT03138889
Link
https://clinicaltrials.gov/study/NCT03138889
Phase
Phase I/II
Status
Terminated
Sponsor
Nektar Therapeutics
More details
This study is to assess the safety and tolerability, and to assess the preliminary clinical benefit of NKTR-214 when combined with pembrolizumab (KEYTRUDA®) with or without chemotherapy. The study is comprised of two groups; dose optimization and dose expansion cohorts. Dose Optimization included first-line and second-line advanced or metastatic solid tumors including non-small cell lung cancer (NSCLC) The dose expansion cohort will include first-line NSCLC patients.
Purpose
Bempegaldesleukin and Pembrolizumab With or Without Chemotherapy in Locally Advanced or Metastatic Solid Tumors
Interventions
Intervention 1
Intervention 2
Intervention 3
Intervention 4
Intervention 5
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2017-06-09
Anticipated Date of Last Follow-up
2023-03-08
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2022-07-05
Actual Completion Date
2022-08-24
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: Dose Optimization and Dose Expansion Inclusion Criteria: * Willing and able to provide written informed consent. * Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF). * Life expectancy \> 12 weeks from the time of enrollment as determined by the Investigator. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Oxygen saturation ≥ 92% on room air for all indications. * Measurable disease per RECIST 1.1. * Patients with brain metastases are eligible if certain criteria are met. * Availability of fresh or archival tumor tissue * Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment Dose Expansion Inclusion Criteria (Non-Small Cell Lung Cancer): * Histol
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
162
Allocation
Not provided
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
PIVOT-02
Identifier
NCT02983045
Link
https://clinicaltrials.gov/study/NCT02983045
Phase
Phase I/II
Status
Completed
Sponsor
Nektar Therapeutics
More details
In this four-part study, NKTR-214 was administered in combination with nivolumab and with/without other anticancer therapies. Part 1 considered escalating doublet (NKTR 214 + nivolumab) doses to determine the RP2D. Part 2 considered dose expansion cohorts for the doublet (NKTR 214 + nivolumab ± chemotherapy). Part 3 was schedule-finding for a triplet therapy (NKTR 214 + nivolumab + ipilimumab). Part 4 dose expansion for the triplet (NKTR 214 + nivolumab + ipilimumab) was planned to further assess the efficacy of the RP2D triplet combination at dosing schedules from Part 3.
Purpose
A Dose Escalation and Cohort Expansion Study of NKTR-214 in Combination With Nivolumab and Other Anti-Cancer Therapies in Patients With Select Advanced Solid Tumors
Interventions
Intervention 1
Intervention 2
Intervention 3
Intervention 4
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2016-12-19
Anticipated Date of Last Follow-up
2023-03-09
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2022-04-28
Actual Completion Date
2022-04-28
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
INCLUSION CRITERIA - For Parts 1-4: * Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) or metastatic solid tumors * Life expectancy \> 12 weeks * Patients must not have received prior interleukin-2 (IL-2) therapy * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Measurable disease per RECIST 1.1 * Patients with stable brain metastases under certain criteria * Fresh and archival tumor tissue available Tumor specific inclusion criteria may apply. EXCLUSION CRITERIA - For Parts 1-4: * Use of an investigational agent or an investigational device within 28 days before administration of first dose of NKTR--214 * Females who are pregnant or breastfeeding * Participants who have an active autoimmune dise
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
557
Allocation
Not provided
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Not provided
Use case
Treatment
Key resources
17239
Identifier
NCT04119557
Link
https://clinicaltrials.gov/study/NCT04119557
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to learn more about the safety of LY3471851 when given by injection just under the skin to participants with psoriasis. The study will last up to 48 weeks and may include up to 23 visits to the study center.
Purpose
A Study of LY3471851 in Participants With Psoriasis
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2019-11-26
Anticipated Date of Last Follow-up
2024-02-16
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2021-07-21
Actual Completion Date
2021-07-21
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Have a confirmed diagnosis of psoriasis for at least 6 months * Have active psoriasis plaques according to study- specific criteria * Be willing and able to undergo skin biopsies Exclusion Criteria: * Have received certain topical medications for psoriasis within 14 days prior to baseline * Have received certain systemic medications for psoriasis within 4 weeks prior to baseline * Have received LY3471851 previously
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
30
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
ATTAIN
Identifier
NCT02915744
Link
https://clinicaltrials.gov/study/NCT02915744
Phase
Phase III
Status
Completed
Sponsor
Nektar Therapeutics
More details
This is an open-label, randomized, active comparator, multicenter, international Phase 3 study of NKTR-102 versus TPC in patients with metastatic breast cancer who have stable brain metastases and have been previously treated with an anthracycline, a taxane, and capecitabine in either the adjuvant or metastatic setting (prior anthracycline may be omitted if medically appropriate or contraindicated for the patient).
Purpose
A Study of Etirinotecan Pegol (NKTR-102) Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With a
Interventions
Intervention 1
Intervention 2
Intervention 3
Intervention 4
Intervention 5
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2016-11-01
Anticipated Date of Last Follow-up
2023-04-10
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2020-07-01
Actual Completion Date
2020-07-01
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Female or male, age ≥ 18 years. * Histologically-confirmed carcinoma of the breast (either the primary or metastatic lesions) for whom single-agent cytotoxic chemotherapy is indicated. Patients may have either measurable or non-measurable disease according to RECIST version 1.1. * Patients must have a history of brain metastases that are non-progressing. * For triple-negative breast cancer, a minimum of 1 prior cytotoxic chemotherapy regimen must have been administered for the indication of metastatic disease.Depending on receptor status, 1 or 2 prior cytotoxic regimens are required prior to enrollment in this trial; hormonal and/or human epidermal growth factor receptor 2 (HER2) -targeted agents may be required. * Have had prior therapy (administered in the neoadjuv
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
178
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
17240
Identifier
NCT04081350
Link
https://clinicaltrials.gov/study/NCT04081350
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to learn more about the safety and side effects of LY3471851 when given by injection just under the skin to participants with eczema. The study will last up to 48 weeks and may include up to 23 visits to the study center.
Purpose
A Study of LY3471851 in Participants With Eczema
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2019-12-04
Anticipated Date of Last Follow-up
2024-02-15
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2022-06-24
Actual Completion Date
2022-06-24
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Have a confirmed diagnosis of atopic dermatitis (AD) for least 12 months * Have active AD according to study specific criteria * Be willing and able to undergo skin biopsies Exclusion Criteria: * Have received certain topical medications for AD within 14 days prior to baseline * Have received certain systemic medications for AD within 4 weeks prior to baseline * Have received LY3471851 previously
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
48
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
INSTRUCT-UC
Identifier
NCT04677179
Link
https://clinicaltrials.gov/study/NCT04677179
Phase
Phase II
Status
Terminated
Sponsor
Nektar Therapeutics
More details
The reason for this study is to determine if the study drug LY3471851 is safe and effective in adult participants with active ulcerative colitis (UC). The study treatment will last about 52 weeks.
Purpose
A Study of LY3471851 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC)
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2021-03-22
Anticipated Date of Last Follow-up
2023-08-08
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2022-08-09
Actual Completion Date
2022-08-09
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Have moderately to severely active ulcerative colitis (UC) as defined by a modified Mayo score (MMS) of 4 to 9 with an endoscopic subscore (ES) ≥2, with endoscopy performed within 14 days before baseline. * Have evidence of UC extending proximal to the rectum (with ≥15 centimeters (cm) of involved colon). * Have up-to-date colorectal cancer surveillance performed according to local standard. * Participants are either one of the following: * Have failed conventional treatments including inability to tolerate oral or intravenous corticosteroids or immunomodulators (6-mercaptopurine or azathioprine or methotrexate), or history of corticosteroid dependence (an inability to successfully taper corticosteroids without return of UC) and neither failed or demonstrated intoler
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
81
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
PIVOT-12
Identifier
NCT04410445
Link
https://clinicaltrials.gov/study/NCT04410445
Phase
Phase III
Status
Terminated
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to compare the efficacy of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA/B/C/D, or Stage IV cutaneous melanoma who are at high risk for recurrence.
Purpose
Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2020-07-27
Anticipated Date of Last Follow-up
2023-03-31
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2022-09-22
Actual Completion Date
2022-09-22
Studied populations
Age Cohort
- Children
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Male or female patients, age 12 years or older at the time of signing the informed consent form (age 18 years or older where local regulations, countries, and/or institutional policies do not allow for patients \< 18 years of age (adolescents) to participate). In regions where adolescents are not allowed to participate in the study due to age restrictions, enrolled patients must be ≥ 18 years of age. * Histologically confirmed Stage IIIA (LN metastasis \> 1 mm), IIIB/C/D, or IV (M1a/b/c/d) cutaneous melanoma by AJCC (8th edition) at study entry that has been completely surgically resected within 12 weeks prior to randomization. * Tumor tissue available from biopsy or resected disease must be provided to central laboratory for PD-L1 status analysis. Must have PD-L1 ex
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
765
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
17-214-09
Identifier
NCT03729245
Link
https://clinicaltrials.gov/study/NCT03729245
Phase
Phase III
Status
Terminated
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to compare the objective response rate (ORR) and overall survival (OS) of bempegaldesleukin (NKTR-214: BEMPEG) combined with nivolumab to that of tyrosine kinase inhibitor (TKI) monotherapy (sunitinib or cabozantinib) in IMDC intermediate- or poor-risk patients and IMDC all-risk patients with previously untreated advanced renal cell carcinoma (RCC).
Purpose
A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Mon
Interventions
Intervention 1
Intervention 2
Intervention 3
Intervention 4
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2018-12-18
Anticipated Date of Last Follow-up
2023-03-17
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2022-01-07
Actual Completion Date
2022-10-19
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Key Inclusion Criteria: * Provide written, informed consent to participate in the study and follow the study procedures * Karnofsky Performance Status (KPS) of at least 70% * Measurable disease per mRECIST 1.1 criteria * Histologically confirmed RCC with a clear-cell component (may have sarcomatoid features); advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC * Patients with any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score (favorable-, intermediate-, or poor-risk) are eligible. At least one IMDC prognostic factor must be present to qualify as either intermediate- or poor-risk renal cell carcinoma. * No prior systemic therapy (including neoadjuvant, adjuvant, or vaccine therapy) for RCC Key Exclusion Criteri
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
623
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Not provided
Use case
Treatment
Key resources
ISLAND-SLE
Identifier
NCT04433585
Link
https://clinicaltrials.gov/study/NCT04433585
Phase
Phase II
Status
Completed
Sponsor
Nektar Therapeutics
More details
The reason for this study is to see if the study drug LY3471851 (NKTR-358) is safe and effective in adults with systemic lupus erythematosus (SLE).
Purpose
A Study of LY3471851 in Adults With Systemic Lupus Erythematosus (SLE)
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2020-08-19
Anticipated Date of Last Follow-up
2024-03-27
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2023-01-10
Actual Completion Date
2023-02-16
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Have a clinical diagnosis of SLE at least 24 weeks prior to screening. * Have documentation of having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 American College of Rheumatology (ACR) criteria for classification of SLE prior to randomization. * Have a positive antinuclear antibody (ANA) (titer ≥1:80) and/or a positive anti-double-stranded deoxyribonucleic acid (dsDNA), and/or a positive anti-Smith (anti-Sm) as assessed by a central laboratory during screening. * Have a total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥6 during screening. * Have a clinical SLEDAI-2K score ≥4 at randomization. * Have active arthritis and/or active rash. Exclusion Crit
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
291
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Studied route(s) of administration
Not provided
Use case
Treatment
Key resources
17238
Identifier
NCT03556007
Link
https://clinicaltrials.gov/study/NCT03556007
Phase
Phase I
Status
Completed
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to evaluate the safety and tolerability of a study drug known as LY3471851 in participants with SLE. The study will last about 79 days for each participant.
Purpose
A Study of NKTR-358 (LY3471851) in Participants With Systemic Lupus Erythematosus (SLE)
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2018-04-18
Anticipated Date of Last Follow-up
2023-11-15
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2019-08-29
Actual Completion Date
2019-08-29
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Willing and able to give written informed consent and comply with study procedures and requirements. * Body mass index (BMI) between 18.0 and 32.0 kilograms per square meter (kg/m²). * Systolic blood pressure between 90 to 140 millimeters of mercury (mm Hg), diastolic blood pressure between 50 to 90 mm Hg, and resting heart rate between 40 to 100 beats per minute. * Diagnosis of adult SLE according to the 1997 ACR classification criteria for at least 6 months prior to signing the informed consent form (ICF). * Minimal to moderate SLE disease activity (active SLE clinical disease is not required for enrollment into the study and participants with severe SLE clinical disease activity, based on the evaluation of the investigator, should be excluded). * If a participant
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
48
Allocation
Randomized
Intervention model
Parallel Assignment
Intervention model description
Not provided
Masking
Double-blind masking
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Use case
Treatment
Key resources
NKTR-214
Identifier
NCT02869295
Link
https://clinicaltrials.gov/study/NCT02869295
Phase
Phase I/II
Status
Completed
Sponsor
Nektar Therapeutics
More details
This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR-214 in adult patients with locally advanced or metastatic solid tumors.
Purpose
A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors
Interventions
Intervention 1
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2015-12-01
Anticipated Date of Last Follow-up
2021-07-09
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2018-10-31
Actual Completion Date
2018-10-31
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Inclusion Criteria: * Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor. * Received 1 or 2 prior lines of therapy. * Life expectancy \>12 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. * Measurable disease per RECIST v1.1. * Demonstrated adequate organ function within 14 days of treatment initiation. * Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior system anticancer therapy, radiotherapy or surgery. * Women of childbearing potential must agree to use highly effective methods of birth control. * All participants must agree to use double barrier contraception during study participation and for at least 2 months after the last dose of study drug. * Additional criteria may apply.
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
28
Allocation
Not provided
Intervention model
Sequential assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Studied LA-formulation(s)
Studied route(s) of administration
Not provided
Use case
Treatment
Key resources
PIVOT-10
Identifier
NCT03785925
Link
https://clinicaltrials.gov/study/NCT03785925
Phase
Phase II
Status
Completed
Sponsor
Nektar Therapeutics
More details
The main purpose of this study is to evaluate the anti-tumor activity of bempegaldesleukin (NKTR-214) in combination with nivolumab by assessing the objective response rate (ORR) in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients.
Purpose
A Single-Arm Study of Bempegaldesleukin (NKTR-214) Plus Nivolumab in Cisplatin Ineligible Patients Who Have Locally Advanced or Metastatic Urothelial Cancer
Interventions
Intervention 1
Intervention 2
Countries
Sites / Institutions
Not provided
Trials dates
Anticipated Start Date
Not provided
Actual Start Date
2019-04-29
Anticipated Date of Last Follow-up
2023-03-27
Estimated Primary Completion Date
Not provided
Estimated Completion Date
Not provided
Actual Primary Completion Date
2022-02-09
Actual Completion Date
2022-06-30
Studied populations
Age Cohort
- Adults
- Older Adults
Genders
- All
Accepts pregnant individuals
Unspecified
Accepts lactating individuals
Unspecified
Accepts healthy individuals
No
Comments about the studied populations
Key Inclusion Criteria: * Provide written, informed consent to participate in the study and follow the study procedures * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 * Measurable disease per RECIST 1.1 criteria * Histologically or cytologically documented inoperable, locally advanced or metastatic urothelial cell carcinoma (also termed TCC) * Fresh biopsy or archival tissue * No prior systemic chemotherapy or investigational agent for inoperable locally advanced or mUC * Ineligible for cisplatin Key Exclusion Criteria: * Patients who have an active, known or suspected autoimmune disease * Patients must not have received prior IL-2 therapy * Prior treatment with an anti PD-1, anti PD-L1, or anti cytotoxic T lymphocyte associated protein 4 (anti CTLA-4) antibody, a
Health status
Not provided
Study type
Interventional (clinical trial)
Enrollment
192
Allocation
Not provided
Intervention model
Single group assignment
Intervention model description
Not provided
Masking
Open label
Masking description
Not provided
Frequency of administration
Not provided
Studied LA-formulation(s)
Not provided
Studied route(s) of administration
Not provided
Use case
Not provided
Key resources
Excipients
Proprietary excipients used
Not provided
Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration
1. Carbohydrates (Monosaccharides; Disaccharides; Polysaccharides; Sugar alcohols (Alditols)) 2. Inorganic Salts (NaCl; KCl; NaSO4; KNO3; Na2PO3/Na2PO4) 3. Antimicrobial Agents (Benzalkonium chloride, Benzethonium chloride, Benzyl alcohol) 4. Antioxidants (Butylated hydroxyanisole (BHA)) 5. Surfactants (Polysorbates, Pluronics) 6. Buffers (Phosphate buffers) 7. Acids (HCL. HPO3, Acetic acid and citric acid) 8. Bases (NaOH, KOH, NH3OH)
Residual solvents used
Not provided
Additional features
Other features of the technology
- Biodegradable
Release properties
The release kinetics of the active pharmaceutical ingredient (API) are influenced by multiple factors, including the chemical stability of the linker (with ester < carbonate < carbamate < amide), local pH conditions, and the presence and activity of relevant enzymes (e.g., esterases and proteases). Additional determinants include PEG arm length and molecular architecture, as well as the degree of drug loading, defined by the number of conjugated arms.
Injectability
This technology is adminstered as intratumoral injection. Intratumoral administration is conducted using a fine-gauge needle (approximately 22–25 gauge), with needle insertion angle and depth selected based on tumor size, location, and imaging guidance, where applicable.
Safety
Rezpegaldesleukin (NKTR-358; REZPEG) is a polyethylene glycol–conjugated recombinant human interleukin-2 (rhIL-2). Phase 2 results show Treatment-emergent adverse events (TEAEs) were reported in 66.0% of subjects receiving REZPEG compared with 48.7% of those receiving placebo, while treatment-related adverse events (TRAEs) occurred in 41.9% and 10.4% of subjects, respectively. Severe TEAEs were reported in 3.2% of subjects in the REZPEG group and 4.5% in the placebo group. The most frequently reported TRAE with REZPEG was injection-site reaction (ISR), occurring in 26.4% of subjects.
Stability
- In situ stability: The stability of the conjugate in circulation is influenced by linker chemistry. Stable linkers (e.g., amides, thioethers) are resistant to hydrolytic cleavage under physiological conditions, whereas releasable linkers undergo gradual cleavage in biological environments. PEG chains (e.g., PEG 20 kDa) enhance aqueous solubility and reduce the risk of drug precipitation. -Formulation stability: Long-term stability studies are typically conducted under controlled conditions (25 °C ± 2 °C / 60% RH ± 5% RH). but no results were disclosed.
Storage conditions and cold-chain related features
1. Refrigeration at 2–8 °C (most PEGylated cytokines) 2. Temperature‑controlled shipping
Potential application(s)
Therapeutic area(s)
Use case(s)
Use of technology
Ease of administration
- Administered by a community health worker
- Administered by a nurse
- Administered by a specialty health worker
Frequency of administration
Monthly, Every 2 weeks, Every 3 weeks
User acceptance
Not provided
Targeted user groups
Age Cohort- Adults
- Older Adults
- All
Pregnant individuals
Unspecified
Lactating individuals
Unspecified
Healthy individuals
Unspecified
Comment
Not provided
Potential associated API(s)
Antineoplastic and immunomodulating agents
Class(es)
IL-2 receptor agonist
Development stage
Phase II
Clinical trial number(s)
NCT06136741
Foreseen/approved indication(s)
Diabetes mellitus type 2 (T2DM), Acute dermatitis and Alopecia Areata
Foreseen user group
Not provided
Foreseen duration between application(s)
Every 2 weeks
Applications to Stringent Regulatory Authorities (SRA) / regulatory approvals
Not approved yet
Antineoplastic and immunomodulating agents
Class(es)
Tumor necrosis factor receptor 2 agonist (TNFR2)
Development stage
Pre-clinical
Clinical trial number(s)
Not provided
Foreseen/approved indication(s)
Ulcerative Colitis, Vitiligo, Multiple Sclerosis
Foreseen user group
Not provided
Foreseen duration between application(s)
Not provided
Applications to Stringent Regulatory Authorities (SRA) / regulatory approvals
Not approved yet
Antineoplastic and immunomodulating agents
Class(es)
Bispecific antibody incorporating TNFR agonist
Development stage
Pre-clinical
Clinical trial number(s)
Not provided
Foreseen/approved indication(s)
Autoimmune Diseases
Foreseen user group
Not provided
Foreseen duration between application(s)
Not provided
Applications to Stringent Regulatory Authorities (SRA) / regulatory approvals
Not approved yet
Antineoplastic and immunomodulating agents
Class(es)
Colony stimulating factor 1 (CSF-1)
Development stage
Pre-clinical
Clinical trial number(s)
Not provided
Foreseen/approved indication(s)
Fibrotic diseases
Foreseen user group
Not provided
Foreseen duration between application(s)
Not provided
Applications to Stringent Regulatory Authorities (SRA) / regulatory approvals
Not approved yet
Antineoplastic and immunomodulating agents
Class(es)
IL-15 receptor agonist
Development stage
Phase II
Clinical trial number(s)
NCT04136756
Foreseen/approved indication(s)
Solid Tumors and Large B-Cell Lymphoma (Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma)
Foreseen user group
Not provided
Foreseen duration between application(s)
Every 3 weeks, every 4 weeks IV infusion
Applications to Stringent Regulatory Authorities (SRA) / regulatory approvals
Not approved yet
Antineoplastic and immunomodulating agents
Class(es)
IL-2 receptor agonist
Development stage
Phase II
Clinical trial number(s)
NCT03138889
Foreseen/approved indication(s)
Locally Advanced or Metastatic Solid Tumors
Foreseen user group
Not provided
Foreseen duration between application(s)
Every 3 weeks
Applications to Stringent Regulatory Authorities (SRA) / regulatory approvals
Not approved yet
Patent info
Description
Multi-arm polymer conjugates of tlr agonist compounds and related immunotherapeutic treatment methods
Brief description
Provided are multi-arm polymer conjugates of Toll-Like Receptor ("TLR") agonists such as TLR 7/8 agonists, as well as related compositions, and methods of making and using such conjugates. Exemplary conjugates are encompassed by Formula I: (I) or a pharmaceutically acceptable salt form thereof, where R, taken together with each Q, is a residue of a polyol, polythiol, or polyamine bearing from 3 to about 50 hydroxyl, thiol, or amino groups; each Q is a linker selected from oxygen, sulfur and -NH; each POLY is independently a water-soluble, non-peptidic polymer; each Xr is independently a linkage-containing spacer moiety; q is a positive integer from 3 to about 50; and each TLR 7/8 AG is a Toll-like receptor 7/8 agonist. Also provided is a method of administering to a patient having cancer.
Representative patent
WO2018132496A1
Category
Not provided
Patent holder
Nektar Therapeutics
Exclusivity
Not provided
Expiration date
October 17, 2019
Status
Ceased
Supporting material
Publications
<p>Silverberg JI, Rosmarin D, Chovatiya R, Bieber T, Schleicher S, Beck L, Gooderham M, Chaudhry S, Fanton C, Yu D, Levy J, Liu Y, Miyazaki T, Tagliaferri M, Schmitz C, Nirula A, Kotzin B, Zalevsky J. The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: two randomized, double-blind, placebo-controlled phase 1b trials. Nat Commun. 2024 Oct 25;15(1):9230. doi: <a target="_blank" rel="noopener noreferrer" href="10.1038/s41467-024-53384-1.">10.1038/s41467-024-53384-1</a>. PMID: 39455575; PMCID: PMC11511931.</p>
Regulatory T cell (Treg) impairment is implicated in the pathogenesis of chronic inflammatory diseases, but relatively little is known about the therapeutic potential of Treg restoration. Here we present clinical evidence for the Treg-selective interleukin-2 receptor agonist rezpegaldesleukin (REZPEG) in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557). Key inclusion criteria for AD included an Eczema Area and Severity Index (EASI) score ≥ 16 and a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and for PsO included a Psoriasis Area and Severity Index (PASI) score of ≥ 12 and a static Physician's Global Assessment (sPGA) score of ≥ 3. REZPEG is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 µg/kg or 24 µg/kg once every 2 weeks for 12 weeks, meeting the primary and secondary objectives, respectively. AD patients receiving the higher dose demonstrate an 83% improvement in EASI score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and vIGA-AD responses are maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. These exploratory clinical improvements are accompanied by sustained increases in CD25bright Tregs. REZPEG thus represents a homeostatic approach to cutaneous disease therapy and holds clinical potential in providing long-term, treatment-free disease control.
<p>Charych DH, Hoch U, Langowski JL, Lee SR, Addepalli MK, Kirk PB, Sheng D, Liu X, Sims PW, VanderVeen LA, Ali CF, Chang TK, Konakova M, Pena RL, Kanhere RS, Kirksey YM, Ji C, Wang Y, Huang J, Sweeney TD, Kantak SS, Doberstein SK. NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models. Clin Cancer Res. 2016 Feb 1;22(3):680-90. doi: 10.1158/1078-0432.CCR-15-1631. PMID: 26832745.</p>
Purpose: Aldesleukin, recombinant human IL2, is an effective immunotherapy for metastatic melanoma and renal cancer, with durable responses in approximately 10% of patients; however, severe side effects limit maximal dosing and thus the number of patients able to receive treatment and potential cure. NKTR-214 is a prodrug of conjugated IL2, retaining the same amino acid sequence as aldesleukin. The IL2 core is conjugated to 6 releasable polyethylene glycol (PEG) chains. In vivo, the PEG chains slowly release to generate active IL2 conjugates.
Experimental design: We evaluated the bioactivity and receptor binding of NKTR-214 and its active IL2 conjugates in vitro; the tumor immunology, tumor pharmacokinetics, and efficacy of NKTR-214 as a single agent and in combination with anti-CTLA-4 antibody in murine tumor models. Tolerability was evaluated in non-human primates.
Results: In a murine melanoma tumor model, the ratio of tumor-killing CD8(+) T cells to Foxp3(+) regulatory T cells was greater than 400 for NKTR-214 compared with 18 for aldesleukin, supporting preferential activation of the IL2 receptor beta over IL2 receptor alpha, due to the location of PEG molecules. NKTR-214 provides a 500-fold greater exposure of the tumor to conjugated IL2 compared with aldesleukin. NKTR-214 showed efficacy as a single agent and provided durable immunity that was resistant to tumor rechallenge in combination with anti-CTLA-4 antibody. NKTR-214 was well tolerated in non-human primates.
Conclusions: These data support further evaluation of NKTR-214 in humans for a variety of tumor types, adding to the repertoire of potent and potentially curative cancer immunotherapies.
Additional documents
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Useful links
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Collaborate for developmentConsider on a case by case basis, collaborating on developing long acting products with potential significant public health impact, especially for low- and middle-income countries (LMICs), utilising the referred to long-acting technology Not provided |
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Share technical information for match-making assessmentProvide necessary technical information to a potential partner, under confidentiality agreement, to enable preliminary assessment of whether specific medicines of public health importance in LMICs might be compatible with the referred to long-acting technology to achieve a public health benefit Not provided |
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Work with MPP to expand access in LMICsIn the event that a product using the referred to long-acting technology is successfully developed, the technology IP holder(s) will work with the Medicines Patent Pool towards putting in place the most appropriate strategy for timely and affordable access in low and middle-income countries, including through licensing Not provided |
Comment & Information
Illustrations
Ex of Multi-Arm Conjugate: 4‑arm‑PEG20k‑CM‑N‑R848 ( PEG Conjugate of TLR7/8 agonist R848 (resiquimod) through a carboxymethyl (CM) linker forming pentaerythritol‑based 20 kDa PEG.
https://patentimages.storage.googleapis.com/d0/8e/55/106dcf8b969314/WO2018132496A1.pdf
Synthesis of 4‑arm‑PEG20k‑CM‑N‑R848
https://patentimages.storage.googleapis.com/d0/8e/55/106dcf8b969314/WO2018132496A1.pdf
R–Q: residue of polyol/polythiol/polyamine (3–50 functional groups; Q = O, S or NH). POLY: water‑soluble non‑peptidic polymer. Xr: linkage-containing spacer. q = 3–5
https://patentimages.storage.googleapis.com/d0/8e/55/106dcf8b969314/WO2018132496A1.pdf