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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 ( PIVOT-02 )

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

INTRODUCTION

  • Org Study ID: 16-214-02
  • Secondary ID: N/A
  • NTC ID: NCT02983045
  • Sponsor: Nektar Therapeutics

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 and ipilimumab 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), metastatic Breast Cancer (mBC) 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 triplet combination of NKTR-214 plus nivolumab and ipilimumab will
be evaluated in select patients with RCC, NSCLC, Melanoma, and UC. In Part 4, the safety and
efficacy of the triplet combination will be evaluated further in select patients with RCC,
NSCLC, Melanoma and UC.

DETAILED DESCRIPTION


NKTR-214 (investigational agent) is an IL-2 pathway agonist designed to target CD122, a
protein which is found on certain immune cells (known as CD8+ T Cells and Natural Killer
Cells) to expand these cells to promote their anti-tumor effects. Nivolumab is a full human
monoclonal antibody that binds to PD-1 (programmed cell death protein 1) on immune cells and
promotes anti-tumor effects. NKTR-214, nivolumab and ipilimumab each target the immune system
differently and may act synergistically to promote anti-cancer effects.

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, mBC 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 include
up to 650 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 and ipilimumab.
During this part of the study, the RP2D triplet combination schedules will be determined in
the following tumor types: RCC, NSCLC, Melanoma, or UC.

Part 4: Dose expansion of triplet combinations of NKTR-214 in combination with nivolumab and
ipilimumab in select tumor types. Each cohort will enroll between 6-36 patients and could
include up to 5275 patients. Enrollment into Part 4 will commence once the RP2D for the
triplet 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.


  • Overall Status
    Recruiting
  • Start Date
    October 2016
  • Phase
    Phase 1/Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Efficacy of NKTR-214 in combination with nivolumab as assessed by the Objective Response Rate (ORR) based on immune-related RECIST (irRECIST) at the RP2D.

Primary Outcome 1 - Timeframe: Through study completion, an expected average of 2 years

Primary Outcome 2 - Measure: Efficacy of NKTR-214 in combination with nivolumab and ipilimumab as assessed by the Objective Response Rate (ORR) based on immune-related RECIST (irRECIST) at the RP2D.

Primary Outcome 2 - Timeframe: Through study completion, an expected average of 2 years

CONDITION

  • Melanoma
  • Renal Cell Carcinoma
  • Non Small Cell Lung Cancer
  • Urothelial Carcinoma
  • Metastatic Breast Cancer
  • Colorectal Cancer

ELIGIBILITY


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

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Corina Andresen, MD

Role: Study Director

Affiliation: Nektar Therapeutics

Overall Contact

Name: Corina Andresen, MD

Phone: 855-482-8676

Email: StudyInquiry@nektar.com

LOCATION

Facility Status Contact
Facility: Local Institution - La Jolla
La Jolla, California 92093
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Los Angeles
Los Angeles, California 90095
United States
Status: Recruiting Contact: N/A
Facility: Local Institution- Palo Alto
Stanford, California 94305
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Aurora
Aurora, Colorado 80045
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - New Haven
New Haven, Connecticut 06473
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Tampa
Tampa, Florida 33612
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Atlanta
Atlanta, Georgia 30322
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Maywood
Maywood, Illinois 60153
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Indianapolis
Indianapolis, Indiana 46202
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Kansas City
Kansas City, Kansas 66205
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Boston
Boston, Massachusetts 02115
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Detroit
Detroit, Michigan 48202
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - St. Louis
Saint Louis, Missouri 63110
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Buffalo
Buffalo, New York 14263
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - New York 1
New York, New York 10016
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - New York 2
New York, New York 10065
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Portland
Portland, Oregon 97213
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Houston
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Fairfax ISC
Fairfax, Virginia 22031
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Fairfax VCS
Fairfax, Virginia 22031
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Seattle
Seattle, Washington 98109
United States
Status: Recruiting Contact: N/A
Facility: Local Institution - Edegem
Edegem, 02650
Belgium
Status: Recruiting Contact: N/A
Facility: Local Institution - Toronto SBH
Toronto, Ontario M4N3M5
Canada
Status: Recruiting Contact: N/A
Facility: Local Institution - Toronto PMH
Toronto, Ontario M5G2M10
Canada
Status: Recruiting Contact: N/A
Facility: Local Institution - Marseille LPC
Marseille, Brouches-duRhone 13009
France
Status: Recruiting Contact: N/A
Facility: Local Institution - Saint-Herblain
Saint-Herblain, Loire-Atlantique 44805
France
Status: Recruiting Contact: N/A
Facility: Local Institution - Lyon
Lyon, 69008
France
Status: Recruiting Contact: N/A
Facility: Local Institution - Marseille HN
Marseille Cedex 20, 13915
France
Status: Recruiting Contact: N/A
Facility: Local Institution - Villejuif Cedex
Villejuif, 94805
France
Status: Recruiting Contact: N/A
Facility: Local Institution - Milano FIIN
Milano, 20133
Italy
Status: Recruiting Contact: N/A
Facility: Local Institution - Roma
Roma, 00152
Italy
Status: Recruiting Contact: N/A
Facility: Local Institution - Siena
Siena, 53100
Italy
Status: Recruiting Contact: N/A
Facility: Local Institution - Buriasco (Turin)
Turin, 10060
Italy
Status: Recruiting Contact: N/A
Facility: Local Institution - Barcelona HQB
Barcelona, 8023
Spain
Status: Recruiting Contact: N/A
Facility: Local Institution - Barcelona HCB
Barcelona, 8036
Spain
Status: Recruiting Contact: N/A
Facility: Local Institution - Madrid HU12
Madrid, 28041
Spain
Status: Recruiting Contact: N/A
Facility: Local Institution - Madrid CIOCC
Madrid, 28050
Spain
Status: Recruiting Contact: N/A
Facility: Local Institution - Pamplona
Pamplona, 31008
Spain
Status: Recruiting Contact: N/A
Facility: Local Institution - Sevilla
Sevilla, 41013
Spain
Status: Recruiting Contact: N/A
Facility: Local Institution - London
London, SM25PT
United Kingdom
Status: Recruiting Contact: N/A
Facility: Local Institution - Northwood
Northwood, HA62RN
United Kingdom
Status: Recruiting Contact: N/A
Facility: Local Institution - Withington
Withington, M204BX
United Kingdom
Status: Recruiting Contact: N/A