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)

March 9, 2023 updated by: Nektar Therapeutics

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

557

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Edegem, Belgium, 02650
        • Antwerp University Hospital
      • Kortrijk, Belgium, 08500
        • Vzw Az Groeninge
      • Leuven, Belgium, 03000
        • UZ Leuven
      • Liège, Belgium, 04000
        • CHU de Liege
      • Wilrijk, Belgium, 02610
        • GZA Ziekenhuizen campus Sint-Augustinus
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, H3T1E2
        • BC Cancer Agency Vancouver Centre
    • Ontario
      • Toronto, Ontario, Canada, M4N3M5
        • Sunnybrook Health Sciences Centre
      • Toronto, Ontario, Canada, M5G2M10
        • Princess Margaret Cancer Centre
    • Quebec
      • Montréal, Quebec, Canada, H3T1E2
        • Jewish General Hospital
  • France
      • Lyon, France, 69008
        • Centre Leon Berard
      • Marseille Cedex 20, France, 13915
        • Assistance Publique Hôpitaux de Marseille - Hôpital Nord
      • Villejuif, France, 94805
        • Gustave Roussy
    • Brouches-duRhone
      • Marseille, Brouches-duRhone, France, 13009
        • L'Institut Paoli - Calmettes
    • Loire-Atlantique
      • Saint-Herblain, Loire-Atlantique, France, 44805
        • Institut de cancerologie de l'ouest
  • Italy
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Milano, Italy, 20141
        • Istituto Europeo di Oncologia
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
      • Roma, Italy, 00152
        • Azienda Ospedaliera San Camillo-Forlanini
      • Siena, Italy, 53100
        • Azienda Ospedaliera Universitaria Senese
      • Turin, Italy, 10060
        • Institute for Cancer Research and Treatment (IRCC)
  • Poland
      • Brzozów, Poland
        • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. Markiewicza
      • Gdynia, Poland, 81519
        • Szpitale Pomorskie Sp. z o.o.
      • Otwock, Poland, 05400
        • Mazowieckie Centrum Leczenia chorób Płuc i Gruźlicy
      • Poznań, Poland, 60569
        • Wielkopolskie Centrum Pulmonologii i Torakochirurgii
      • Poznań, Poland, 60693
        • Med-Polonia Sp. z o.o.
      • Łódź, Poland, 93509
        • Instytut Medyczny Santa Familia Sp. z o. o. w Łodzi
  • Spain
      • Barcelona, Spain, 8036
        • Hospital Clínic de Barcelona
      • Barcelona, Spain, 8023
        • Hospital Quiron Barcelona
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28050
        • Centro Integral Oncológico Clara Campal (CIOCC)
      • Pamplona, Spain, 31008
        • Clinica Universidad de Navarra
      • Sevilla, Spain, 41013
        • Campus Hospital Universitario Virgen del Rocío - Instituto de Biomedicina de Sevilla (IBIS)
  • United Kingdom
      • London, United Kingdom, SM25PT
        • The Royal Marsden NHS Trust
      • Northwood, United Kingdom, HA62RN
        • Mount Vernon Cancer Centre
      • Withington, United Kingdom, M204BX
        • The Christie NHS Foundation Trust
  • United States
    • California
      • La Jolla, California, United States, 92093
        • UCSD, Moores Cancer Center
      • Los Angeles, California, United States, 90095
        • UCLA
      • Stanford, California, United States, 94305
        • Stanford Cancer Institute
    • Colorado
      • Denver, Colorado, United States, 80045
        • University of Colorado, Denver
    • Connecticut
      • New Haven, Connecticut, United States, 06473
        • Yale School of Medicine
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Orlando, Florida, United States, 32806
        • Orlando Health Inc.
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center, Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health Melvin & Bren Simon Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66205
        • University of Kansas Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine in St. Louis
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • New York University Langone Medical Center - NYU Cancer Institute
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC
      • Fairfax, Virginia, United States, 22031
        • Inova Fairfax Hospital
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Dose Escalation Doublet: Combination of NKTR-214 + nivolumab
NKTR 214 + nivolumab at 5 dosage levels.
Other Names:
  • Bempegaldesleukin + Opdivo®
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.
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:
  • Bempegaldesleukin+ Opdivo®
  • Carboplatin (Paraplatin®)
  • Cisplatin (Platinol®)
  • Pemetrexed (Alimta®)
  • Paclitaxel (Taxol®)
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).
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 Names:
  • Bempegaldesleukin+ Opdivo®+ Yervoy®
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.
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 Names:
  • Bempegaldesleukin+ Opdivo®+ Yervoy®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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 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.
Dose-limiting toxicities (DLTs) were assessed during a 3-week (21-day) DLT evaluation period beginning with the first dose of ipilimumab.
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.
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.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Within 3 years from study start
Overall survival is defined as the time from date of first dose to the date of death
Within 3 years from study start
Progression-Free Survival (PFS)
Time Frame: Through study completion, an expected average of 2 years
PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause.
Through study completion, an expected average of 2 years
Clinical Benefit Rate (CBR)
Time Frame: Within 3 years from study start
CBR will be assessed as the number of subjects with a BOR of Complete Response (CR), confirmed Partial Response (PR), or Stable Disease (SD) (where the duration of SD should be ≥ 84 days) divided by the total number of subjects in the Response Evaluable Population
Within 3 years from study start
Duration of Response (DOR)
Time Frame: Through study completion, an expected average of 2 years
DOR is defined as time between the date of first radiographic images that documented objective response and the date of the first radiographic images that documented disease progression.
Through study completion, an expected average of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nektar Therapeutics

Collaborators

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 19, 2016

Primary Completion (Actual)

April 28, 2022

Study Completion (Actual)

April 28, 2022

Study Registration Dates

First Submitted

November 23, 2016

First Submitted That Met QC Criteria

December 1, 2016

First Posted (Estimate)

December 6, 2016

Study Record Updates

Last Update Posted (Actual)

March 13, 2023

Last Update Submitted That Met QC Criteria

March 9, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-214-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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