Clinical Trial 19109

Cancer Type: Genitourinary
Interventions:BMS-936558 (Nivolumab); NKTR-214; Nivolumab

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Mayer Fishman

Overview

Study Title

A Phase 1/2, Open-label, Multicenter, Dose Escalation and Dose Expansion Study of NKTR-214 and Nivolumab in Patients with Select Locally Advanced or Metastatic Solid Tumor Malignancies

Summary

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.

Objective

The Primary Objectives are: - To evaluate the safety and tolerability, and define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of NKTR-214 in combination with nivolumab. - To evaluate the efficacy of NKTR-214 in combination with nivolumab by assessing the objective response rate (ORR) by RECIST 1.1 at the RP2D. The SecondaryOobjectives are: - To evaluate the efficacy of NKTR-214 in combination with nivolumab by assessing overall survival (OS) and progression-free survival (PFS). The Exploratory Objectives are: - To evaluate the efficacy of NKTR-214 in combination with nivolumab by assessing immune-related RECIST (irRECIST) at the RP2D. - To assess the immunological effects, and to accommodate disease-specific pharmacodynamics markers such as lactate dehydrogenase (LDH) (e.g., in melanoma), of NKTR-214 when administered in combination with nivolumab. - To characterize the pharmacokinetics (PK) of nivolumab and NKTR-214 and metabolites. - To assess the development of anti-drug antibodies against NKTR-214 and nivolumab when administered in combination. - To assess the association between efficacy measures and PD-L1 expression in tumors.

Inclusion Criteria

  • Histologically confirmed diagnosis of a locally advanced or metastatic melanoma, renal cell carcinoma (RCC), or non-small 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
  • Participants 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
  • 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
  • Potential participants with stable brain metastases may be enrolled if certain criteria are met
  • Sample of archival tumor tissue and fresh baseline tumor biopsies are required
  • Additional criteria may apply

  • Exclusion Criteria

  • 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
  • Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis
  • Prior surgery or radiotherapy within 14 days of therapy
  • Participants who have had less than 28 days since the last chemotherapy, biological therapy, or less than 14 days from approved tyrosine kinase inhibitor (TKI) therapy (sunitinib, sorafenib, vemurafenib, dabrafenib, cobimetinib), or systemic or inhaled steroid therapy at doses greater than 10mg of prednisone or equivalent before administration of the first dose of study medication. > Participants' inability to adhere to or tolerate protocol or study procedures.
  • Additional criteria may apply