Brief Title
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
Official Title
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
Brief 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.
Detailed Description
The study is designed in four parts.
Part 1: Dose escalation of NKTR-214 in combination with nivolumab. Part 1 has been completed
and the recommended phase 2 dose (RP2D) has been identified, which is being studied further
in Parts 2, 3 and 4 of the study.
Part 2: Dose expansion of NKTR-214 in combination with nivolumab. Patients with the following
tumor types (Melanoma, RCC, NSCLC, UC, triple negative breast cancer (TNBC), HR+/HER2- breast
cancer, gastric cancer, and CRC) will be enrolled to receive the RP2D of NKTR-214 in
combination with nivolumab. In addition, NKTR-214 with nivolumab and other anti-cancer
therapies including cytotoxic chemotherapy will be evaluated in select patients with NSCLC.
Each cohort in Part 2 has a target enrollment of 12-36 patients and could add up to a total
of 936 patients who are either checkpoint-therapy naïve or anti-PD-1 or anti-PD-L1
relapsed/refractory. One dedicated and separate cohort in Part 2 will evaluate NKTR-214 with
nivolumab in an additional 100 second-line NSCLC patients previously treated with an
anti-PD-1 or anti-PD-L1 in combination with doublet platinum-containing cytotoxic
chemotherapy in first-line.
Part 3: Schedule and safety finding of NKTR-214 in combination with nivolumab. During this
part of the study, the RP2D doublet combination schedules will be determined in the following
tumor types: RCC, NSCLC, Melanoma, or UC.
Part 4: Dose expansion of doublet combinations of NKTR-214 in combination with nivolumab in
select tumor types. Each cohort will enroll between 6-36 patients and could include up to 106
patients. Enrollment into Part 4 will commence once the RP2D for the doublet combination has
been established in Part 3 for each respective tumor type.
All patients enrolled in the study will be closely monitored for safety, tolerability and
response per RECIST criteria. The primary efficacy endpoint of the combination will be
assessed using objective response rate (ORR). Exploratory immunological biomarkers in plasma
and tumor samples will evaluate immune activation.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Incidence of drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs leading to discontinuation, deaths, and laboratory abnormalities associated with use of NKTR-214 in combination with nivolumab and or other anti-cancer therapies
Secondary Outcome
Overall Survival (OS)
Condition
Melanoma
Intervention
Combination of NKTR-214 + nivolumab
Study Arms / Comparison Groups
Dose Escalation: Combination of NKTR-214 + nivolumab
Description: NKTR-214 in escalating doses will be combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
557
Start Date
December 19, 2016
Completion Date
April 28, 2022
Primary Completion Date
April 28, 2022
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Study Director, ,
Location Countries
Belgium
Location Countries
Belgium
Administrative Informations
NCT ID
NCT02983045
Organization ID
16-214-02
Responsible Party
Sponsor
Study Sponsor
Nektar Therapeutics
Collaborators
Bristol-Myers Squibb
Study Sponsor
Study Director, Study Director, Nektar Therapeutics
Verification Date
June 2022