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 ( PIVOT-02 )

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 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.

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window

Condition

Melanoma

Intervention

Dose Escalation Doublet: Combination of NKTR-214 + nivolumab

Study Arms / Comparison Groups

 Dose Escalation: Combination of NKTR-214 + nivolumab

Description:  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.

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

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

March 2023