Last updated on October 2018

A Dose Escalation and Cohort Expansion Study of CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 Antibody (Nivolumab) or in Combination With Nivolumab and Anti-CTLA4 Antibody (Ipilimumab) in Patients With Select Advanced or Metastatic Solid Tumors


Brief description of study

In this four part study, NKTR-214 will be administered in combination with nivolumab in Parts 1 & 2, and with nivolumab and ipilimumab in Parts 3 & 4. In Part 1, the safety, efficacy and recommended Phase 2 dose (RP2D) of NKTR-214 in combination with nivolumab will be determined. In Part 2, the clinical benefit, safety, and tolerability of combining NKTR-214 with nivolumab at the RP2D in select patients with Melanoma, Renal Cell Carcinoma, Non-Small Cell Lung Cancer, Urothelial Carcinoma, or Triple Negative Breast Cancer. In Part 3, the safety, efficacy and RP2D of NKTR-214 in combination with nivolumab and ipilimumab will be determined. In Part 4, the clinical benefit, safety, and tolerability of the triplet combination will be evaluated in select patients with RCC or NSCLC. All three drugs target the immune system and may act synergistically to promote anti-cancer effects.

Detailed Study Description

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 (programmed cell death protein 1) on immune cells and promotes anti-tumor effects.

Part 1: Dose escalation of NKTR-214 in combination with nivolumab. A total of 38 eligible patients were enrolled into one of five dose regimens of NKTR-214 in combination with nivolumab (0.006 mg/kg NKTR-214 every 3 weeks (q3w) with 240 mg nivolumab every two weeks (q2w), 0.003 mg/kg NKTR-214 q2w with 240 mg nivolumab q2w, 0.006 mg/kg NKTR-214 q2w with 240 mg nivolumab q2w, 0.006 mg/kg NKTR-214 q3w with 360 mg nivolumab q3w, 0.009 mg/kg NKTR-214 q3w with 360 mg nivolumab q3w). The first part of the study evaluated the safety and efficacy profile of the combination and it was determined that a dose of 0.006 mg/kg NKTR-214 q3w with 360 mg nivolumab q3w, was the Recommended Phase 2 Dose (RP2D), to be studied in Part 2 of the study.

Part 2: Dose expansion of NKTR-214 in combination with nivolumab. Patients across a total of five specific tumor types (Melanoma, Renal Cell Carcinoma (RCC), Non-Small Cell Lung Cancer (NSCLC), Urothelial Carcinoma, and Triple Negative Breast Cancer (TNBC)) will be enrolled to receive the RP2D of NKTR-214 in combination with nivolumab. Approximately 350 eligible patients who are either Immuno-oncology (I-O) therapy nave or anti-PD-1 or anti-PD-L1 relapsed/refractory will be enrolled in the Dose Expansion (Part 2) into one of thirteen cohorts as follows:

  • Melanoma:1st-line
  • Melanoma: 2nd- and 3rd-line anti-PD-1 or anti-PD-L1 relapsed/refractory
  • RCC: 1st-line I-O therapy nave
  • RCC: 2nd- and 3rd-line anti-PD-1 or anti-PD-L1 relapsed/refractory
  • NSCLC 1st-line (PD-L1 50%)
  • NSCLC 1st-line (PD-L1< 1%)
  • NSCLC 1st-line (PD-L1 1% - < 50%)
  • NSCLC: 2nd-line I-O therapy nave
  • NSCLC: 2nd- and 3rd-line anti-PD-1 or anti-PD-L1 relapsed/refractory
  • Urothelial Carcinoma (Bladder): 1st-line I-O therapy nave
  • Urothelial Carcinoma (Bladder): 1st-line cisplatin-ineligible I-O therapy nave
  • Urothelial Carcinoma (Bladder): 3rd-Line anti-PD-1 or anti-PD-L1 relapsed/refractory
  • TNBC: 1st- and 2nd-line I-O therapy nave

Part 3: Schedule finding of NKTR-214 in combination with nivolumab and ipilimumab. During this part of the study, the safety and tolerability, and efficacy of the triplet combination will be evaluated in approximately 30 treatment nave patients with metastatic RCC or NSCLC to determine a RP2D and administration schedule. The first schedule to be evaluated Cohort A, is NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w with the addition of ipilimumab 1 mg/kg q6w.

Part 4: Dose expansion of NKTR-214 in combination with nivolumab and ipilimumab. Approximately 60 first line RCC or NSCLC patients (26-38 patients per indication) will be enrolled at the RP2D determined in Part 3 to further evaluate the safety, tolerability and efficacy of the triple combination.

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). Exploratory immunological biomarkers in plasma and tumor samples will evaluate immune activation.

Clinical Study Identifier: NCT02983045

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Recruitment Status: Open


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