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

NCT02983045 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 16-214-02
• Study Type: interventional
• Target: 557
• Locations: 8 countries
• Sites: 58

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.

Conditions

Melanoma; Renal Cell Carcinoma; Non Small Cell Lung Cancer; Urothelial Carcinoma; Triple Negative Breast Cancer; HR+/HER2- Breast Cancer; Gastric Cancer

Keywords

NKTR-214; Bempegaldesleukin; Nivolumab; Paclitaxel; Carboplatin; Cisplatin; Pemetrexed; Melanoma; Renal Cell Carcinoma; Non Small Cell Lung Cancer; Urothelial Carcinoma; Triple Negative Breast Cancer; HR+/HER2- Breast Cancer; Gastric Cancer; Colorectal Cancer; Metastatic; Advanced; Immunotherapy; Anti-PD-1; anti-CTLA-4

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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.

Study Arms (4)

Dose Escalation: Combination of NKTR-214 + nivolumab

EXPERIMENTAL

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

Dose Expansion: Combination of NKTR-214 + nivolumab

EXPERIMENTAL

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

Experimental: Combination of NKTR-214 + nivolumab + ipilimumab

EXPERIMENTAL

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

Experimental: Dose Expansion of Part 3

EXPERIMENTAL

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

Interventions

Dose Escalation Doublet: Combination of NKTR-214 + nivolumab DRUG

NKTR 214 + nivolumab at 5 dosage levels.

Also known as: Bempegaldesleukin + Opdivo®

Dose Escalation: Combination of NKTR-214 + nivolumab

Dose Expansion Doublet: Combination of NKTR-214 + nivolumab DRUG

Select patient cohorts with select tumor types will be dosed with NKTR-214 + nivolumab at the RP2D + other anti-cancer therapies per institution standard.

Also known as: Bempegaldesleukin+ Opdivo®, Carboplatin (Paraplatin®), Cisplatin (Platinol®), Pemetrexed (Alimta®), Paclitaxel (Taxol®)

Dose Expansion: Combination of NKTR-214 + nivolumab

Schedule Finding Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab DRUG

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.

Also known as: Bempegaldesleukin+ Opdivo®+ Yervoy®

Experimental: Combination of NKTR-214 + nivolumab + ipilimumab

Dose Expansion Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab DRUG

Combination of NKTR-214 + nivolumab + ipilimumab was administered at RP2D dose/schedules in select tumor types

Also known as: Bempegaldesleukin+ Opdivo®+ Yervoy®

Experimental: Dose Expansion of Part 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nektar Therapeutics: lead
• Bristol-Myers Squibb: collaborator

Study Sites (58)

UCSD, Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

University of Colorado, Denver

Denver, Colorado, 80045, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06473, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Orlando Health Inc.

Orlando, Florida, 32806, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Loyola University Medical Center, Chicago

Maywood, Illinois, 60153, United States

Location

Indiana University Health Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66205, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York University Langone Medical Center - NYU Cancer Institute

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Inova Fairfax Hospital

Fairfax, Virginia, 22031, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Antwerp University Hospital

Edegem, 02650, Belgium

Location

Vzw Az Groeninge

Kortrijk, 08500, Belgium

Location

UZ Leuven

Leuven, 03000, Belgium

Location

CHU de Liège

Liège, 04000, Belgium

Location

GZA Ziekenhuizen Campus Sint-Augustinus

Wilrijk, 02610, Belgium

Location

BC Cancer Agency Vancouver Centre

Vancouver, British Columbia, H3T1E2, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M10, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

L'Institut Paoli - Calmettes

Marseille, Brouches-duRhone, 13009, France

Location

Institut de Cancerologie de l'Ouest

Saint-Herblain, Loire-Atlantique, 44805, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Assistance Publique Hopitaux de Marseille - Hopital Nord

Marseille, 13915, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Napoli, 80131, Italy

Location

Azienda Ospedaliera San Camillo-Forlanini

Roma, 00152, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

Institute for Cancer Research and Treatment (IRCC)

Turin, 10060, Italy

Location

Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza

Brzozów, Poland

Location

Szpitale Pomorskie Sp. z o.o.

Gdynia, 81519, Poland

Location

Instytut Medyczny Santa Familia Sp. z o. o. w Łodzi

Lodz, 93509, Poland

Location

Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy

Otwock, 05400, Poland

Location

Wielkopolskie Centrum Pulmonologii i Torakochirurgii

Poznan, 60569, Poland

Location

Med-Polonia Sp. z o.o.

Poznan, 60693, Poland

Location

Hospital Quirón Barcelona

Barcelona, 8023, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 8036, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Centro Integral Oncológico Clara Campal (CIOCC)

Madrid, 28050, Spain

Location

Clínica Universidad de Navarra

Pamplona, 31008, Spain

Location

Campus Hospital Universitario Virgen del Rocío - Instituto de Biomedicina de Sevilla (IBIS)

Seville, 41013, Spain

Location

The Royal Marsden NHS Trust

London, SM25PT, United Kingdom

Location

Mount Vernon Cancer Centre

Northwood, HA62RN, United Kingdom

Location

The Christie NHS Foundation Trust

Withington, M204BX, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 35643589 DERIVED

• 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.

  PMID: 34255535 DERIVED

• 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.

  PMID: 33298619 DERIVED

MeSH Terms

Conditions

Melanoma; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell; Triple Negative Breast Neoplasms; Stomach Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis

Interventions

Nivolumab; bempegaldesleukin; Carboplatin; Cisplatin; Pemetrexed; Paclitaxel

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Study Director
• Organization: Nektar Therapeutics

StudyInquiry@nektar.com

855-482-8676

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2016
• First Posted: December 6, 2016
• Study Start: December 19, 2016
• Primary Completion: April 28, 2022
• Study Completion: April 28, 2022
• Last Updated: March 13, 2023
• Results First Posted: March 13, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (7); FR (5); GB (3); CA (4); BE (5); PL (6); IT (6); US (22)