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

Gastric Cancer Clinical Trial

— PIVOT-02  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02983045
• Other study ID #: 16-214-02
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 19, 2016
• Est. completion date: April 28, 2022

Study information

• Verified date: March 2023
• Source: Nektar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 557
• Est. completion date: April 28, 2022
• Est. primary completion date: April 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Carcinoma, Transitional Cell
• Gastric Cancer
• Melanoma
• Non Small Cell Lung Cancer
• Renal Cell Carcinoma
• Stomach Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urothelial Carcinoma

Intervention

Drug:
• Dose Escalation Doublet: Combination of NKTR-214 + nivolumab
NKTR 214 + nivolumab at 5 dosage levels.
• 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.
• 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.
• 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

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital	Edegem
Belgium	Vzw Az Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	CHU de Liège	Liège
Belgium	GZA Ziekenhuizen Campus Sint-Augustinus	Wilrijk
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BC Cancer Agency Vancouver Centre	Vancouver	British Columbia
France	Centre Léon Bérard	Lyon
France	L'Institut Paoli - Calmettes	Marseille	Brouches-duRhone
France	Assistance Publique Hopitaux de Marseille - Hopital Nord	Marseille Cedex 20
France	Institut de Cancerologie de l'Ouest	Saint-Herblain	Loire-Atlantique
France	Gustave Roussy	Villejuif
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"	Napoli
Italy	Azienda Ospedaliera San Camillo-Forlanini	Roma
Italy	Azienda Ospedaliera Universitaria Senese	Siena
Italy	Institute for Cancer Research and Treatment (IRCC)	Turin
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza	Brzozów
Poland	Szpitale Pomorskie Sp. z o.o.	Gdynia
Poland	Instytut Medyczny Santa Familia Sp. z o. o. w Lodzi	Lódz
Poland	Mazowieckie Centrum Leczenia Chorób Pluc i Gruzlicy	Otwock
Poland	Med-Polonia Sp. z o.o.	Poznan
Poland	Wielkopolskie Centrum Pulmonologii i Torakochirurgii	Poznan
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Quirón Barcelona	Barcelona
Spain	Centro Integral Oncológico Clara Campal (CIOCC)	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Campus Hospital Universitario Virgen del Rocío - Instituto de Biomedicina de Sevilla (IBIS)	Sevilla
United Kingdom	The Royal Marsden NHS Trust	London
United Kingdom	Mount Vernon Cancer Centre	Northwood
United Kingdom	The Christie NHS Foundation Trust	Withington
United States	Emory University Hospital	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Colorado, Denver	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Inova Fairfax Hospital	Fairfax	Virginia
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	University of Florida	Gainesville	Florida
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Health Melvin & Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	UCSD, Moores Cancer Center	La Jolla	California
United States	UCLA	Los Angeles	California
United States	Loyola University Medical Center, Chicago	Maywood	Illinois
United States	Yale School of Medicine	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	New York University Langone Medical Center - NYU Cancer Institute	New York	New York
United States	Orlando Health Inc.	Orlando	Florida
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Stanford Cancer Institute	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Nektar Therapeutics	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window	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.	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.
Primary	Part 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window	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.	Dose-limiting toxicities (DLTs) were assessed during a 3-week (21-day) DLT evaluation period beginning with the first dose of ipilimumab.
Primary	Part 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D)	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.	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.