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 (PIVOT-02)
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| ClinicalTrials.gov Identifier: NCT02983045 |
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Recruitment Status :
Completed
First Posted : December 6, 2016
Results First Posted : March 13, 2023
Last Update Posted : March 13, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Melanoma Renal Cell Carcinoma Non Small Cell Lung Cancer Urothelial Carcinoma Triple Negative Breast Cancer HR+/HER2- Breast Cancer Gastric Cancer | Drug: Dose Escalation Doublet: Combination of NKTR-214 + nivolumab Drug: Dose Expansion Doublet: Combination of NKTR-214 + nivolumab Drug: Schedule Finding Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab Drug: Dose Expansion Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 557 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2, Open-label, Multicenter Study of the Combination of NKTR-214 and Nivolumab or the Combination of NKTR-214, Nivolumab, and Other Anti-Cancer Therapies in Patients With Select Locally Advanced or Metastatic Solid Tumor Malignancies |
| Actual Study Start Date : | December 19, 2016 |
| Actual Primary Completion Date : | April 28, 2022 |
| Actual Study Completion Date : | April 28, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation: Combination of NKTR-214 + nivolumab
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.
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Drug: Dose Escalation Doublet: Combination of NKTR-214 + nivolumab
NKTR 214 + nivolumab at 5 dosage levels.
Other Name: Bempegaldesleukin + Opdivo® |
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Experimental: Dose Expansion: Combination of NKTR-214 + nivolumab
NKTR-214+nivolumab in patients with advanced or metastatic solid tumor malignancies to assess the efficacy of the RP2D.
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Drug: Dose Expansion Doublet: Combination of NKTR-214 + nivolumab
Select patient cohorts with select tumor types will be dosed with NKTR-214 + nivolumab at the RP2D + other anti-cancer therapies per institution standard.
Other Names:
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Experimental: Experimental: Combination of NKTR-214 + nivolumab + ipilimumab
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).
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Drug: Schedule Finding Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab
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.
Other Name: Bempegaldesleukin+ Opdivo®+ Yervoy® |
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Experimental: Experimental: Dose Expansion of Part 3
To further assess the RP2D triplet combination dosing schedules from Part 3 in 1L NSCLC and 1L RCC patients.
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Drug: Dose Expansion Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab
Combination of NKTR-214 + nivolumab + ipilimumab was administered at RP2D dose/schedules in select tumor types
Other Name: Bempegaldesleukin+ Opdivo®+ Yervoy® |
- 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. ]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.
- 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. ]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.
- 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. ]
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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02983045
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| Study Director: | Study Director | Nektar Therapeutics |
Documents provided by Nektar Therapeutics:
| Responsible Party: | Nektar Therapeutics |
| ClinicalTrials.gov Identifier: | NCT02983045 |
| Other Study ID Numbers: |
16-214-02 |
| First Posted: | December 6, 2016 Key Record Dates |
| Results First Posted: | March 13, 2023 |
| Last Update Posted: | March 13, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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NKTR-214 Bempegaldesleukin Nivolumab Paclitaxel Carboplatin Cisplatin Pemetrexed Melanoma Renal Cell Carcinoma Non Small Cell Lung Cancer |
Urothelial Carcinoma Triple Negative Breast Cancer HR+/HER2- Breast Cancer Gastric Cancer Colorectal Cancer Metastatic Advanced Immunotherapy Anti-PD-1 anti-CTLA-4 |
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Carcinoma Breast Neoplasms Carcinoma, Non-Small-Cell Lung Melanoma Stomach Neoplasms Carcinoma, Renal Cell Triple Negative Breast Neoplasms Carcinoma, Transitional Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Lung Neoplasms |
Respiratory Tract Neoplasms Thoracic Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Nevi and Melanomas Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases |