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)

Nektar Therapeutics

Status and phase: Completed; Phase 2; Phase 1

Conditions: HR+/HER2- Breast Cancer; Melanoma; Gastric Cancer; Urothelial Carcinoma; Non Small Cell Lung Cancer; Triple Negative Breast Cancer; Renal Cell Carcinoma

Treatments: Drug: Dose Expansion Doublet: Combination of NKTR-214 + nivolumab; Drug: Schedule Finding Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab; Drug: Dose Escalation Doublet: Combination of NKTR-214 + nivolumab; Drug: Dose Expansion Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02983045

16-214-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 557 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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557 participants in 4 patient groups

Dose Escalation: Combination of NKTR-214 + nivolumab

Experimental group

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.

Treatment:

Drug: Dose Escalation Doublet: Combination of NKTR-214 + nivolumab

Dose Expansion: Combination of NKTR-214 + nivolumab

Experimental group

Description:

NKTR-214+nivolumab in patients with advanced or metastatic solid tumor malignancies to assess the efficacy of the RP2D.

Treatment:

Drug: Dose Expansion Doublet: Combination of NKTR-214 + nivolumab

Experimental: Combination of NKTR-214 + nivolumab + ipilimumab

Experimental group

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).

Treatment:

Drug: Schedule Finding Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab

Experimental: Dose Expansion of Part 3

Experimental group

Description:

To further assess the RP2D triplet combination dosing schedules from Part 3 in 1L NSCLC and 1L RCC patients.

Treatment:

Drug: Dose Expansion Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab