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)
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|ClinicalTrials.gov Identifier: NCT02983045|
Recruitment Status : Recruiting
First Posted : December 6, 2016
Last Update Posted : February 28, 2018
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Renal Cell Carcinoma Non Small Cell Lung Cancer Urothelial Carcinoma Triple Negative Breast Cancer||Drug: Combination of NKTR-214 + nivolumab||Phase 1 Phase 2|
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.
A total of 38 eligible patients were enrolled in the Dose Escalation portion of the study (Part 1) and were assigned to 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.
During the Dose Expansion portion of the study (Part 2), 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 330 eligible patients who are either Immuno-oncology (I-O) therapy naïve 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: 2nd- and 3rd-line anti-PD-1 or anti-PD-L1 relapsed/refractory
- RCC: 1st-line I-O therapy naïve
- 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 naïve
- NSCLC: 2nd- and 3rd-line anti-PD-1 or anti-PD-L1 relapsed/refractory
- Urothelial Carcinoma (Bladder): 1st-line I-O therapy naïve
- Urothelial Carcinoma (Bladder): 1st-line cisplatin-ineligible I-O therapy naïve
- Urothelial Carcinoma (Bladder): 3rd-Line anti-PD-1 or anti-PD-L1 relapsed/refractory
- TNBC: 1st- and 2nd-line I-O therapy naïve
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||330 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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.|
|Actual Study Start Date :||October 2016|
|Estimated Primary Completion Date :||October 2018|
|Estimated Study Completion Date :||October 2018|
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 1 of the study is to find the RP2D.
For Part 2 of the study, enrollment into a dose expansion cohort will commence once the 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
Part 1: Patients with select tumor types will receive NKTR-214 doses administered either q3w or q2w, in combination with 240 mg nivolumab q2w or in combination with 360 mg of nivolumab q3w.
Part 2: Additional patient cohorts with select tumor types will be dosed at the RP2D dose/schedule of NKTR-214 and nivolumab (as determined by Part 1 of the trial).
Other Name: NKTR-214 + Opdivo®
- 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: 90 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: 90 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02983045
|Contact: Nektar Recruitment||855-482-8676||StudyInquiry@nektar.com|
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|Study Director:||Michael Imperiale, MD||Nektar Therapeutics|