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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Status: Active

Description

In this four-part study, NKTR-214 will be administered in combination with nivolumab in Part 1, in combination with nivolumab with or without various chemotherapies in Part 2, and with nivolumab and ipilimumab in Parts 3 & 4. In Part 1, the Recommended Phase 2 Dose (RP2D) of NKTR-214 in combination with nivolumab will be determined. In Part 2, NKTR-214 with nivolumab at the RP2D will be evaluated as first-line therapy and / or as second or third line therapy in select patients with Melanoma, Renal Cell Carcinoma (RCC), Non-Small Cell Lung Cancer (NSCLC), Urothelial Carcinoma (UC), metastatic Breast Cancer (mBC) and Colorectal Cancer (CRC). In addition, in Part 2, the RP2D of NKTR-214 with nivolumab and various chemotherapies and regimens in select cohorts of NSCLC patients will be determined. In Part 3, several different regimens of the triplet combination of NKTR-214 plus nivolumab and ipilimumab will be evaluated in select patients with RCC, NSCLC, Melanoma, and UC. In Part 4, the safety and efficacy of the triplet combination will be evaluated further in select patients with RCC, NSCLC, Melanoma and UC.

Eligibility Criteria

Inclusion 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

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: Active
Contact: Thu Ly
Phone: 310-794-3860
Email: tply@mednet.ucla.edu
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Name Not Available
San Diego
University of California San Diego
Status: Active
Name Not Available

Colorado

Aurora
University of Colorado Hospital
Status: Active
Name Not Available

Connecticut

New Haven
Yale University
Status: Active
Name Not Available

Florida

Tampa
Moffitt Cancer Center
Status: Active
Name Not Available

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available

Illinois

Chicago
Northwestern University
Status: Active
Name Not Available

Kansas

Fairway
University of Kansas Clinical Research Center
Status: Active
Name Not Available
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: Active
Name Not Available

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: Approved
Name Not Available
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Name Not Available
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: Active
Name Not Available
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available

North Carolina

Durham
Duke University Medical Center
Status: Active
Name Not Available

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: Active
Name Not Available

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: Active
Name Not Available

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: Active
Name Not Available

Trial Objectives and Outline

NKTR-214 (investigational agent) is an IL-2 pathway agonist designed to target CD122, a protein which is found on certain immune cells (known as CD8+ T Cells and Natural Killer Cells) to expand these cells to promote their anti-tumor effects. Nivolumab is a full human monoclonal antibody that binds to PD-1 (programmed cell death protein 1) on immune cells and promotes anti-tumor effects. NKTR-214, nivolumab and ipilimumab each target the immune system differently and may act synergistically to promote anti-cancer effects. The study is designed in four parts. Part 1: Dose escalation of NKTR-214 in combination with nivolumab. Part 1 has been completed and the recommended phase 2 dose (RP2D) has been identified, which is being studied further in Parts 2, 3 and 4 of the study. Part 2: Dose expansion of NKTR-214 in combination with nivolumab. Patients with the following tumor types (Melanoma, RCC, NSCLC, UC, mBC and CRC) will be enrolled to receive the RP2D of NKTR-214 in combination with nivolumab. In addition, NKTR-214 with nivolumab and other anti-cancer therapies including cytotoxic chemotherapy will be evaluated in select patients with NSCLC. Each cohort in Part 2 has a target enrollment of 12-36 patients and could include up to 650 patients who are either checkpoint-therapy naïve or anti-PD-1 or anti-PD-L1 relapsed/refractory. One dedicated and separate cohort in Part 2 will evaluate NKTR-214 with nivolumab in an additional 100 second-line NSCLC patients previously treated with an anti-PD-1 or anti-PD-L1 in combination with doublet platinum-containing cytotoxic chemotherapy in first-line. Part 3: Schedule and safety finding of NKTR-214 in combination with nivolumab and ipilimumab. During this part of the study, the RP2D triplet combination schedules will be determined in the following tumor types: RCC, NSCLC, Melanoma, or UC. Part 4: Dose expansion of triplet combinations of NKTR-214 in combination with nivolumab and ipilimumab in select tumor types. Each cohort will enroll between 6-36 patients and could include up to 5275 patients. Enrollment into Part 4 will commence once the RP2D for the triplet combination has been established in Part 3 for each respective tumor type. All patients enrolled in the study will be closely monitored for safety, tolerability and response per RECIST criteria. The primary efficacy endpoint of the combination will be assessed using objective response rate (ORR). Exploratory immunological biomarkers in plasma and tumor samples will evaluate immune activation.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Nektar

Trial IDs

Primary ID 16-214-02
Secondary IDs NCI-2017-00053
Clinicaltrials.gov ID NCT02983045