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NCT02983045 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
COMPLETED
Registry last update
2023-03-13

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window

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outcome · POSTED

Part 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window

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outcome · POSTED

Part 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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 disease requiring systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents * History of organ transplant that requires use of immune suppressive agents * Active malignancy not related to the current diagnosed malignancy * Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis * Participants who have had \< 28 days since the last chemotherapy, biological therapy, or \< 14 days from approved tyrosine kinase inhibitor (TKI) therapy, or systemic or inhaled steroid therapy at doses greater than 10mg of prednisone Tumor specific exclusion criteria may apply. Other protocol defined inclusion/exclusion criteria may apply
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    NKTR 214 + nivolumab at 5 dosage levels to determine the RP2D Part 1 of RP2D in patients with advanced or metastatic melanoma, RCC, NSCLC, urothelial carcinoma, or TNBC.
    intervention Names
    1. Drug: Dose Escalation Doublet: Combination of NKTR-214 + nivolumab
    label
    Dose Escalation: Combination of NKTR-214 + nivolumab
    type
    EXPERIMENTAL
  2. description
    NKTR-214+nivolumab in patients with advanced or metastatic solid tumor malignancies to assess the efficacy of the RP2D.
    intervention Names
    1. Drug: Dose Expansion Doublet: Combination of NKTR-214 + nivolumab
    label
    Dose Expansion: Combination of NKTR-214 + nivolumab
    type
    EXPERIMENTAL
  3. description
    To assess the safety and tolerability of NKTR 214 + nivolumab + ipilimumab triplet therapy and establish RP2D dosing schedules for Part 4 in patients with advanced or metastatic melanoma, RCC, NSCLC, or UCC in a first-line setting (1L).
    intervention Names
    1. Drug: Schedule Finding Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab
    label
    Experimental: Combination of NKTR-214 + nivolumab + ipilimumab
    type
    EXPERIMENTAL
  4. description
    To further assess the RP2D triplet combination dosing schedules from Part 3 in 1L NSCLC and 1L RCC patients.
    intervention Names
    1. Drug: Dose Expansion Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab
    label
    Experimental: Dose Expansion of Part 3
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Dose Escalation: Combination of NKTR-214 + nivolumab
    description
    NKTR 214 + nivolumab at 5 dosage levels.
    name
    Dose Escalation Doublet: Combination of NKTR-214 + nivolumab
    other Names
    1. Bempegaldesleukin + Opdivo®
    type
    DRUG
  2. arm Group Labels
    1. Dose Expansion: Combination of NKTR-214 + nivolumab
    description
    Select patient cohorts with select tumor types will be dosed with NKTR-214 + nivolumab at the RP2D + other anti-cancer therapies per institution standard.
    name
    Dose Expansion Doublet: Combination of NKTR-214 + nivolumab
    other Names
    1. Bempegaldesleukin+ Opdivo®
    2. Carboplatin (Paraplatin®)
    3. Cisplatin (Platinol®)
    4. Pemetrexed (Alimta®)
    5. Paclitaxel (Taxol®)
    type
    DRUG
  3. arm Group Labels
    1. Experimental: Combination of NKTR-214 + nivolumab + ipilimumab
    description
    1L patients with RCC, NSCLC, UCC, and melanoma received NKTR-214 0.006 mg/kg q3w in combination with nivolumab and ipilimumab according to 3 dosing schedules.
    name
    Schedule Finding Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab
    other Names
    1. Bempegaldesleukin+ Opdivo®+ Yervoy®
    type
    DRUG
  4. arm Group Labels
    1. Experimental: Dose Expansion of Part 3
    description
    Combination of NKTR-214 + nivolumab + ipilimumab was administered at RP2D dose/schedules in select tumor types
    name
    Dose Expansion Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab
    other Names
    1. Bempegaldesleukin+ Opdivo®+ Yervoy®
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
557
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Part 1of the study was a dose-escalation phase that evaluated the safety and tolerability and defined the maximum tolerated dose or recommended Phase 2 dose of the NKTR-214/nivolumab doublet across 5 dosage/schedule levels. The results presented are for the DLT Population.
    measure
    Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window
    time Frame
    Includes DLTs that occurred within the DLT window of at least 21 days after the first dose of study treatment (28 days for every 2 weeks dosing; 21 days for every 3 weeks dosing). Patients were counted only once under each preferred term.
  2. description
    Part 3 of the study was a schedule finding phase to establish the recommended phase 2 dosing schedules for Part 4 and assess the safety and tolerability for the NKTR-214/nivolumab/ipilimumab triplet combination. The results presented are for the DLT Population.
    measure
    Part 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window
    time Frame
    Dose-limiting toxicities (DLTs) were assessed during a 3-week (21-day) DLT evaluation period beginning with the first dose of ipilimumab.
  3. description
    Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) at Recommended Phase 2 Dose (RP2D). ORR is defined as the percentage of enrolled participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.
    measure
    Part 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D)
    time Frame
    Tumor assessment at Screening then every 8 weeks (± 7 days) from Cycle 1 Day 1 and end of treatment (unless scan done within 4 weeks) up to approximately 27 months.
Full study description
brief Summary
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.
detailed Description
Part 1 enrolled patients with advanced or metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), urothelial carcinoma, or triple negative breast cancer (TNBC) to determine the recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD) of NKTR 214 + nivolumab doublet therapy. Part 2 enrolled patients with advanced or metastatic solid tumor malignancies (including 9 tumor types consisting of the same 5 tumor types as in Part 1, plus hormone receptor positive human epidermal growth factor receptor 2 \[HER 2\] negative breast cancer \[HR+ HER2- BC\], gastric cancer, colorectal carcinoma, and small cell lung cancer \[SCLC\]) to assess the efficacy of the RP2D. Part 3 enrolled patients with advanced or metastatic melanoma, RCC, NSCLC, or urothelial carcinoma (UCC) in a first-line setting (1L) to assess the safety and tolerability of NKTR 214 + nivolumab + ipilimumab triplet therapy Three dosing schedules were evaluated to establish RP2D dosing schedules for Part 4 of the study. Part 4 planned to enroll patients with advanced or metastatic melanoma, RCC, NSCLC, or UCC to further assess the efficacy of the RP2D triplet combination at the 3 dosing schedules from Part 3. Patients were enrolled simultaneously to each tumor cohort. All patients enrolled in the study were closely monitored for safety, tolerability and response per RECIST criteria. The primary efficacy endpoint was objective response rate (ORR) using RECIST 1.1 at the RP2D doublet.
Source references
references
  1. citation
    Bautista J, Echeverria CE, Maldonado-Noboa I, Adatty-Molina J, Suarez Urresta S, Coral-Riofrio EC, Araujo-Abad S, Kyriakidis NC, Lopez-Cortes A. Next-Generation Immune Checkpoints and Tumor Microenvironment Modulation in Cancer Immunotherapy. J Immunol Res. 2026;2026(1):e7864229. doi: 10.1155/jimr/7864229.
    pmid
    41811823
    type
    DERIVED
  2. citation
    Siefker-Radtke AO, Cho DC, Diab A, Sznol M, Bilen MA, Balar AV, Grignani G, Puente E, Tang L, Chien D, Hoch U, Choudhury A, Yu D, Currie SL, Tagliaferri MA, Zalevsky J, Hurwitz ME, Tannir NM. Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02. Eur Urol. 2022 Oct;82(4):365-373. doi: 10.1016/j.eururo.2022.05.002. Epub 2022 May 25.
    pmid
    35643589
    type
    DERIVED
  3. citation
    Diab A, Tykodi SS, Daniels GA, Maio M, Curti BD, Lewis KD, Jang S, Kalinka E, Puzanov I, Spira AI, Cho DC, Guan S, Puente E, Nguyen T, Hoch U, Currie SL, Lin W, Tagliaferri MA, Zalevsky J, Sznol M, Hurwitz ME. Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma. J Clin Oncol. 2021 Sep 10;39(26):2914-2925. doi: 10.1200/JCO.21.00675. Epub 2021 Jul 13.
    pmid
    34255535
    type
    DERIVED
  4. citation
    Veatch JR, Singhi N, Jesernig B, Paulson KG, Zalevsky J, Iaccucci E, Tykodi SS, Riddell SR. Mobilization of pre-existing polyclonal T cells specific to neoantigens but not self-antigens during treatment of a patient with melanoma with bempegaldesleukin and nivolumab. J Immunother Cancer. 2020 Dec;8(2):e001591. doi: 10.1136/jitc-2020-001591.
    pmid
    33298619
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice