A Dose Escalation and Cohort Expansion Study of CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 Antibody (Nivolumab) in Patients With Select Advanced or Metastatic Solid Tumors (PIVOT-02)
|Carcinoma，Non-Small-Cell Lung Carcinoma, Renal Cell Melanoma||Drug: Combination of NKTR-214 + nivolumab||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official 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.|
- Safety of NKTR-214 in combination with nivolumab as evaluated by incidence of drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation, deaths, and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
- Tolerability of NKTR-214 in combination with nivolumab as evaluated by incidence of Dose Limiting Toxicities (DLTs), drug-related AEs, SAEs, adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
- Efficacy of NKTR-214 in combination with nivolumab as assessed by the Objective Response Rate (ORR) based on RECIST 1.1 [ Time Frame: Through study completion, an expected average of 2 years ]ORR will be measured by the number and percentage of patients achieving a complete or partial response as best overall response and as defined by RECIST 1.1
- Best Overall Response (BOR) in the population of interest [ Time Frame: Through study completion, an expected average of 2 years ]
- Duration Of Response (DOR) [ Time Frame: Through study completion, an expected average of 2 years ]It is defined as time between the date of first radio-graphic images that documented objective response and the date of the first radio-graphic images that documented disease progression.
- Progression-Free Survival (PFS) [ Time Frame: Through study completion, an expected average of 2 years ]PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause
- Clinical Benefit Rate (CBR) [ Time Frame: Through study completion, an expected average of 2 years ]Clinical benefit rate will be assessed as the number of subjects with a BOR of Complete Response (CR), confirmed Partial Response (PR), or Stable Disease (SD) (where the duration of SD should be ≥ 84 days) divided by the total number of subjects in the Response Evaluable Population
- Median Time to Response (MTR) [ Time Frame: Through study completion, an expected average of 2 years ]The median time to response will be summarized descriptively for subjects who have a CR or PR
- Overall Survival (OS) [ Time Frame: Within 3 years from study start ]Overall survival is defined as the time from date of first dose to the date of death
- Efficacy of NKTR-214 in combination with nivolumab by immune-related RECIST (irRECIST) at the RP2D. [ Time Frame: Through study completion, an expected average of 2 years ]
|Actual Study Start Date:||October 2016|
|Estimated Study Completion Date:||October 2018|
|Estimated Primary Completion Date:||October 2018 (Final data collection date for primary outcome measure)|
Experimental: Combination of NKTR-214 + nivolumab
NKTR-214 in escalating doses, will be combined with one of the two proposed doses of nivolumab. The goal of this dose escalation part of the study is to find the recommended phase 2 dose.
For the second part of the study, enrollment into a dose expansion cohort will commence once the Recommended Phase 2 Dose (RP2D) is established for this combination.
Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects.
Drug: Combination of NKTR-214 + nivolumab
Phase 1: Patients with select tumor types will receive NKTR-214 doses administered either every 21 days or every 14 days, in combination with 240 mg nivolumab (Opdivo®) every 14 days or in combination with 360 mg of nivolumab every 21 days.
Phase 2: Additional patient cohorts with select tumor types will be dosed at the recommended Phase 2 dose/schedule of NKTR-214 and nivolumab (as determined by Phase 1 of the trial).
Other Name: NKTR-214 + Opdivo®
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 40 eligible patients that enroll in the dose escalation portion of the study (Phase 1) will be assigned to one of five dose regimens of NKTR-214 in combination with nivolumab (0.006 mg/kg NKTR-214 every 21 days with 240 mg nivolumab every 14 days, 0.003 mg/kg NKTR-214 every 14 days with 240 mg nivolumab every 14 days, 0.006 mg/kg NKTR-214 every 14 days with 240 mg nivolumab every 14 days, 0.006 mg/kg NKTR-214 every 21 days with 360 mg nivolumab every 21 days, 0.003 mg/kg NKTR-214 every 21 days with 360 mg nivolumab every 21 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 in combination with nivolumab.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02983045
|Contact: Nektar Recruitment||855-482-8676||StudyInquiry@nektar.com|
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|Study Director:||Michael Imperiale, MD||Nektar Therapeutics|