Breast Cancer Clinical Trial
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
Summary
In this four-part study, NKTR-214 will be administered in combination with nivolumab in Part 1, in combination with nivolumab with or without various chemotherapies in Part 2, and with nivolumab in Parts 3 & 4. In Part 1, the Recommended Phase 2 Dose (RP2D) of NKTR-214 in combination with nivolumab will be determined. In Part 2, NKTR-214 with nivolumab at the RP2D will be evaluated as first-line therapy and/or as second or third line therapy in select patients with Melanoma, Renal Cell Carcinoma (RCC), Non-Small Cell Lung Cancer (NSCLC), Urothelial Carcinoma (UC), triple negative Breast Cancer (TNBC), HR+/HER2- breast cancer, gastric cancer, and Colorectal Cancer (CRC). In addition, in Part 2, the RP2D of NKTR-214 with nivolumab and various chemotherapies and regimens in select cohorts of NSCLC patients will be determined. In Part 3, several different regimens of the doublet combination of NKTR-214 plus nivolumab will be evaluated in select patients with RCC, NSCLC, Melanoma, and UC. In Part 4, the safety and efficacy of the doublet combination will be evaluated further in select patients with RCC, NSCLC, Melanoma and UC.
Full 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.
Eligibility Criteria
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
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There are 55 Locations for this study
La Jolla California, 92093, United States
Los Angeles California, 90095, United States
Stanford California, 94305, United States
Denver Colorado, 80045, United States
New Haven Connecticut, 06473, United States
Gainesville Florida, 32610, United States
Orlando Florida, 32806, United States
Atlanta Georgia, 30322, United States
Maywood Illinois, 60153, United States
Indianapolis Indiana, 46202, United States
Kansas City Kansas, 66205, United States
Boston Massachusetts, 02115, United States
Detroit Michigan, 48202, United States
Saint Louis Missouri, 63110, United States
Buffalo New York, 14263, United States
New York New York, 10016, United States
New York New York, 10065, United States
Portland Oregon, 97213, United States
Houston Texas, 77030, United States
Fairfax Virginia, 22031, United States
Fairfax Virginia, 22031, United States
Seattle Washington, 98109, United States
Edegem , 02650, Belgium
Kortrijk , 08500, Belgium
Leuven , 03000, Belgium
Liège , 04000, Belgium
Wilrijk , 02610, Belgium
Vancouver British Columbia, H3T1E, Canada
Toronto Ontario, M4N3M, Canada
Toronto Ontario, M5G2M, Canada
Montréal Quebec, H3T1E, Canada
Marseille Brouches-duRhone, 13009, France
Saint-Herblain Loire-Atlantique, 44805, France
Lyon , 69008, France
Marseille Cedex 20 , 13915, France
Villejuif , 94805, France
Milano , 20133, Italy
Milano , 20141, Italy
Napoli , 80131, Italy
Roma , 00152, Italy
Siena , 53100, Italy
Turin , 10060, Italy
Brzozów , , Poland
Gdynia , 81519, Poland
Otwock , 05400, Poland
Poznań , 60569, Poland
Poznań , 60693, Poland
Åódź , 93509, Poland
Barcelona , 8023, Spain
Barcelona , 8036, Spain
Madrid , 28034, Spain
Madrid , 28041, Spain
Madrid , 28050, Spain
Pamplona , 31008, Spain
Sevilla , 41013, Spain
London , SM25P, United Kingdom
Northwood , HA62R, United Kingdom
Withington , M204B, United Kingdom
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