A Phase 1/2, Open-Label, Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of CD122-Biased Cytokine (NKTR-214) and Anti-PD-1 Antibody (Nivolumab) in Patients With Select Locally Advanced or Metastatic Solid Tumor Malignancies

This study is to determine first, the recommended Phase 2 dose of NKTR-214 when administered in combination with nivolumab, and then, the clinical benefit, safety, and tolerability of combining NKTR-214 with nivolumab in select patients with melanoma, renal cell carcinoma or non-small cell lung cancer. Both drugs target the immune system and may act synergistically to promote anti-cancer effects.

NKTR-214 is a cytokine (investigational agent) that is 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 a molecule called PD-1 on immune cells and promotes anti-tumor effects.

Approximately 30 eligible patients that enroll in the dose escalation portion of the study (Phase 1) will be assigned to one of three dose regimens of NKTR-214 (0.006 mg/kg every 21 days, 0.003 mg/kg every 14 days, or 0.006 mg/kg every 14 days) in combination with 240 mg of nivolumab every 14 days. Based on safety, tolerability and efficacy observed in the trial, enrollment to additional dose escalation cohorts are planned. The first phase of the study will test the safety and efficacy profile of the combination and determine which dose will be studied in Phase 2 of the overall study. During Phase 2, cohorts of patients with specific cancers will be expanded and these patients will receive the recommended Phase 2 dose and schedule of NKTR-214 (as determined by Phase 1) in combination with 240 mg of nivolumab every 14 days.

All patients enrolled in the study will be closely monitored to determine if there is response to the treatment as well as for any side effects that may occur. The efficacy of the combination will be assessed using objective response rate (ORR). Immunological biomarkers in plasma and tumor samples will evaluate immune activation.

Inclusion Criteria:
• Histologically confirmed diagnosis of a locally advanced or metastatic melanoma, renal cell carcinoma (RCC), or nonsmall cell lung cancer (NSCLC)
• Melanoma - Advanced or metastatic Melanoma who are treatment naive and are known BRAF wild-type.
• Renal Cell Carcinoma (RCC) - Advanced or metastatic RCC who have received only 1 prior anti-angiogenic therapy, or patient refuses standard of care. Must not have received prior immunotherapy with specified immunomodulators.
• Non-Small Cell Lung Cancer (NSCLC) - Advanced or metastatic NSCLC lacking EGFR-sensitizing mutation and/or ALK translocation. Must have experienced disease recurrence or progression during or after 1 prior platinum doublet-based chemotherapy regimen or patient refuses standard of care. Must not have received prior immunotherapy with specified immunomodulators.
• Life expectancy >12 weeks
• Patients must not have received prior interleukin 2 (IL 2) therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Measurable disease per RECIST 1.1
• Demonstrated adequate organ function within 14 days of treatment initiation
• Oxygen saturation ≥ 92% on room air. NSCLC patients may use supplemental oxygen
• Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior system anticancer therapy, radiotherapy, or surgery
• Women of childbearing potential must agree to use highly effective methods of birth control. All participants must agree to use double barrier contraception during study participation for at least 3 months after the last dose of study drugs
• Patients with stable brain metastases may be enrolled if certain criteria are met
-Sample of archival tumor tissue and fresh baseline tumor biopsies are required

Phase I/II
Multiple Tumor Types
Brendan Curti, M.D.
Nektar Therapeutics
Tara Foote
  • Oncology and Hematology Care Eastside