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
- Conditions
- MelanomaTriple Negative Breast CancerNon Small Cell Lung CancerRenal Cell CarcinomaUrothelial CarcinomaHR+/HER2- Breast CancerGastric Cancer
- Registration Number
- NCT02983045
- Lead Sponsor
- Nektar Therapeutics
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 557
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Part 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window 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.
Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window 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.
Part 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D) 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (58)
CHU de Liège
🇧🇪Liège, Belgium
Mount Vernon Cancer Centre
🇬🇧Northwood, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Withington, United Kingdom
The Royal Marsden NHS Trust
🇬🇧London, United Kingdom
University of Florida
🇺🇸Gainesville, Florida, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
New York University Langone Medical Center - NYU Cancer Institute
🇺🇸New York, New York, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Antwerp University Hospital
🇧🇪Edegem, Belgium
Vzw Az Groeninge
🇧🇪Kortrijk, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
GZA Ziekenhuizen Campus Sint-Augustinus
🇧🇪Wilrijk, Belgium
BC Cancer Agency Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
L'Institut Paoli - Calmettes
🇫🇷Marseille, Brouches-duRhone, France
Centre Léon Bérard
🇫🇷Lyon, France
Institut de Cancerologie de l'Ouest
🇫🇷Saint-Herblain, Loire-Atlantique, France
Assistance Publique Hopitaux de Marseille - Hopital Nord
🇫🇷Marseille Cedex 20, France
Gustave Roussy
🇫🇷Villejuif, France
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹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, Italy
Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
🇵🇱Brzozów, Poland
Stanford Cancer Institute
🇺🇸Stanford, California, United States
UCSD, Moores Cancer Center
🇺🇸La Jolla, California, United States
Szpitale Pomorskie Sp. z o.o.
🇵🇱Gdynia, Poland
Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy
🇵🇱Otwock, Poland
Med-Polonia Sp. z o.o.
🇵🇱Poznań, Poland
Washington University School of Medicine in St. Louis
🇺🇸Saint Louis, Missouri, United States
Wielkopolskie Centrum Pulmonologii i Torakochirurgii
🇵🇱Poznań, Poland
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Hospital Quirón Barcelona
🇪🇸Barcelona, Spain
Instytut Medyczny Santa Familia Sp. z o. o. w Łodzi
🇵🇱Łódź, Poland
Hospital Clínic de Barcelona
🇪🇸Barcelona, 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)
🇪🇸Sevilla, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
UCLA
🇺🇸Los Angeles, California, United States
University of Colorado, Denver
🇺🇸Denver, Colorado, 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
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, 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
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Orlando Health Inc.
🇺🇸Orlando, Florida, United States