A Dose Escalation and Cohort Expansion Study of NKTR-214 in Combination With Nivolumab and Other Anti-Cancer Therapies in Patients With Select Advanced Solid Tumors ( PIVOT-02 )
- INCLUSION CRITERIA - For Parts 1-4: - Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) or metastatic solid tumors - Life expectancy > 12 weeks - Patients must not have received prior interleukin-2 (IL-2) therapy - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Measurable disease per RECIST 1.1 - Patients with stable brain metastases under certain criteria - Fresh and archival tumor tissue available Tumor specific inclusion criteria may apply. EXCLUSION CRITERIA - For Parts 1-4: - 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 - Active malignancy not related to the current diagnosed malignancy - Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis - Participants who have had < 28 days since the last chemotherapy, biological therapy, or < 14 days from approved tyrosine kinase inhibitor (TKI) therapy, or systemic or inhaled steroid therapy at doses greater than 10mg of prednisone Tumor specific exclusion criteria may apply. Other protocol defined inclusion/exclusion criteria may apply
NKTR-214 (investigational agent) is an IL-2 pathway agonist 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 PD-1 (programmed cell death protein 1) on immune cells and promotes anti-tumor effects. NKTR-214, nivolumab and ipilimumab each target the immune system differently and may act synergistically to promote anti-cancer effects. The study is designed in four parts. Part 1: Dose escalation of NKTR-214 in combination with nivolumab. Part 1 has been completed and the recommended phase 2 dose (RP2D) has been identified, which is being studied further in Parts 2, 3 and 4 of the study. Part 2: Dose expansion of NKTR-214 in combination with nivolumab. Patients with the following tumor types (Melanoma, RCC, NSCLC, UC, mBC and CRC) will be enrolled to receive the RP2D of NKTR-214 in combination with nivolumab. In addition, NKTR-214 with nivolumab and other anti-cancer therapies including cytotoxic chemotherapy will be evaluated in select patients with NSCLC. Each cohort in Part 2 has a target enrollment of 12-36 patients and could include up to 650 patients who are either checkpoint-therapy naïve or anti-PD-1 or anti-PD-L1 relapsed/refractory. One dedicated and separate cohort in Part 2 will evaluate NKTR-214 with nivolumab in an additional 100 second-line NSCLC patients previously treated with an anti-PD-1 or anti-PD-L1 in combination with doublet platinum-containing cytotoxic chemotherapy in first-line. Part 3: Schedule and safety finding of NKTR-214 in combination with nivolumab and ipilimumab. During this part of the study, the RP2D triplet combination schedules will be determined in the following tumor types: RCC, NSCLC, Melanoma, or UC. Part 4: Dose expansion of triplet combinations of NKTR-214 in combination with nivolumab and ipilimumab in select tumor types. Each cohort will enroll between 6-36 patients and could include up to 5275 patients. Enrollment into Part 4 will commence once the RP2D for the triplet combination has been established in Part 3 for each respective tumor type. All patients enrolled in the study will be closely monitored for safety, tolerability and response per RECIST criteria. The primary efficacy endpoint of the combination will be assessed using objective response rate (ORR). Exploratory immunological biomarkers in plasma and tumor samples will evaluate immune activation.
Trial Phase Phase I/II
Trial Type Treatment
- Primary ID 16-214-02
- Secondary IDs NCI-2017-00053
- Clinicaltrials.gov ID NCT02983045