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 )

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.

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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