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
NCT ID: NCT02983045
Last Updated: 2023-03-13
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
557 participants
INTERVENTIONAL
2016-12-19
2022-04-28
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
Dose Escalation Doublet: Combination of NKTR-214 + nivolumab
NKTR 214 + nivolumab at 5 dosage levels.
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.
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.
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).
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.
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.
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
Interventions
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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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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Bristol-Myers Squibb
INDUSTRY
Nektar Therapeutics
INDUSTRY
Responsible Party
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Principal Investigators
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Study Director
Role: STUDY_DIRECTOR
Nektar Therapeutics
Locations
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UCSD, Moores Cancer Center
La Jolla, California, United States
UCLA
Los Angeles, California, United States
Stanford Cancer Institute
Stanford, California, United States
University of Colorado, Denver
Denver, Colorado, United States
Yale School of Medicine
New Haven, Connecticut, United States
University of Florida
Gainesville, Florida, United States
Orlando Health Inc.
Orlando, Florida, United States
Emory University Hospital
Atlanta, Georgia, United States
Loyola University Medical Center, Chicago
Maywood, Illinois, United States
Indiana University Health Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
Washington University School of Medicine in St. Louis
St Louis, Missouri, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
New York University Langone Medical Center - NYU Cancer Institute
New York, New York, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Providence Portland Medical Center
Portland, Oregon, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Inova Fairfax Hospital
Fairfax, Virginia, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
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, , Belgium
BC Cancer Agency Vancouver Centre
Vancouver, British Columbia, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Jewish General Hospital
Montreal, Quebec, Canada
L'Institut Paoli - Calmettes
Marseille, Brouches-duRhone, France
Institut de Cancerologie de l'Ouest
Saint-Herblain, Loire-Atlantique, France
Centre Léon Bérard
Lyon, , France
Assistance Publique Hopitaux de Marseille - Hopital Nord
Marseille, , France
Gustave Roussy
Villejuif, , France
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, , Italy
Istituto Europeo di Oncologia
Milan, , 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, , Italy
Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
Brzozów, , Poland
Szpitale Pomorskie Sp. z o.o.
Gdynia, , Poland
Instytut Medyczny Santa Familia Sp. z o. o. w Łodzi
Lodz, , Poland
Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy
Otwock, , Poland
Wielkopolskie Centrum Pulmonologii i Torakochirurgii
Poznan, , Poland
Med-Polonia Sp. z o.o.
Poznan, , Poland
Hospital Quirón Barcelona
Barcelona, , Spain
Hospital Clínic de Barcelona
Barcelona, , Spain
Hospital Universitario Ramón y Cajal
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Centro Integral Oncológico Clara Campal (CIOCC)
Madrid, , Spain
Clínica Universidad de Navarra
Pamplona, , Spain
Campus Hospital Universitario Virgen del Rocío - Instituto de Biomedicina de Sevilla (IBIS)
Seville, , Spain
The Royal Marsden NHS Trust
London, , United Kingdom
Mount Vernon Cancer Centre
Northwood, , United Kingdom
The Christie NHS Foundation Trust
Withington, , United Kingdom
Countries
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References
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Siefker-Radtke AO, Cho DC, Diab A, Sznol M, Bilen MA, Balar AV, Grignani G, Puente E, Tang L, Chien D, Hoch U, Choudhury A, Yu D, Currie SL, Tagliaferri MA, Zalevsky J, Hurwitz ME, Tannir NM. Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02. Eur Urol. 2022 Oct;82(4):365-373. doi: 10.1016/j.eururo.2022.05.002. Epub 2022 May 25.
Diab A, Tykodi SS, Daniels GA, Maio M, Curti BD, Lewis KD, Jang S, Kalinka E, Puzanov I, Spira AI, Cho DC, Guan S, Puente E, Nguyen T, Hoch U, Currie SL, Lin W, Tagliaferri MA, Zalevsky J, Sznol M, Hurwitz ME. Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma. J Clin Oncol. 2021 Sep 10;39(26):2914-2925. doi: 10.1200/JCO.21.00675. Epub 2021 Jul 13.
Veatch JR, Singhi N, Jesernig B, Paulson KG, Zalevsky J, Iaccucci E, Tykodi SS, Riddell SR. Mobilization of pre-existing polyclonal T cells specific to neoantigens but not self-antigens during treatment of a patient with melanoma with bempegaldesleukin and nivolumab. J Immunother Cancer. 2020 Dec;8(2):e001591. doi: 10.1136/jitc-2020-001591.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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16-214-02
Identifier Type: -
Identifier Source: org_study_id
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