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 ) (PIVOT-02)
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ClinicalTrials.gov Identifier: NCT02983045 |
Recruitment Status :
Active, not recruiting
First Posted : December 6, 2016
Last Update Posted : January 5, 2021
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Tracking Information | |||||
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First Submitted Date ICMJE | November 23, 2016 | ||||
First Posted Date ICMJE | December 6, 2016 | ||||
Last Update Posted Date | January 5, 2021 | ||||
Actual Study Start Date ICMJE | December 19, 2016 | ||||
Estimated Primary Completion Date | November 2021 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | 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 ) | ||||
Official Title ICMJE | A Phase 1/2, Open-label, Multicenter Study of the Combination of NKTR-214 and Nivolumab or the Combination of NKTR-214, Nivolumab, and Other Anti-Cancer Therapies in Patients With Select Locally Advanced or Metastatic Solid Tumor Malignancies | ||||
Brief Summary | In this four-part study, NKTR-214 will be administered in combination with nivolumab in Part 1, in combination with nivolumab with or without various chemotherapies in Part 2, and with nivolumab and ipilimumab in Parts 3 & 4. In Part 1, the Recommended Phase 2 Dose (RP2D) of NKTR-214 in combination with nivolumab will be determined. In Part 2, NKTR-214 with nivolumab at the RP2D will be evaluated as first-line therapy and/or as second or third line therapy in select patients with Melanoma, Renal Cell Carcinoma (RCC), Non-Small Cell Lung Cancer (NSCLC), Urothelial Carcinoma (UC), metastatic Breast Cancer (mBC) and Colorectal Cancer (CRC). In addition, in Part 2, the RP2D of NKTR-214 with nivolumab and various chemotherapies and regimens in select cohorts of NSCLC patients will be determined. In Part 3, several different regimens of the triplet combination of NKTR-214 plus nivolumab and ipilimumab will be evaluated in select patients with RCC, NSCLC, Melanoma, and UC. In Part 4, the safety and efficacy of the triplet combination will be evaluated further in select patients with RCC, NSCLC, Melanoma and UC. | ||||
Detailed Description | 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 a total of 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 106 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. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Veatch JR, Singhi N, Jesernig B, Paulson KG, Zalevsky J, Iaccucci E, Tykodi SS, Riddell SR. Mobilization of pre-existing polyclonal T cells specific to neoantigens but not self-antigens during treatment of a patient with melanoma with bempegaldesleukin and nivolumab. J Immunother Cancer. 2020 Dec;8(2). pii: e001591. doi: 10.1136/jitc-2020-001591. Erratum in: J Immunother Cancer. 2021 Feb;9(2):. | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Active, not recruiting | ||||
Estimated Enrollment ICMJE |
557 | ||||
Original Estimated Enrollment ICMJE |
30 | ||||
Estimated Study Completion Date ICMJE | December 2021 | ||||
Estimated Primary Completion Date | November 2021 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | INCLUSION CRITERIA - For Parts 1-4:
EXCLUSION CRITERIA - For Parts 1-4:
Other protocol defined inclusion/exclusion criteria may apply |
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | Belgium, Canada, France, Italy, Poland, Spain, United Kingdom, United States | ||||
Removed Location Countries | Ukraine | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT02983045 | ||||
Other Study ID Numbers ICMJE | 16-214-02 | ||||
Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Nektar Therapeutics | ||||
Study Sponsor ICMJE | Nektar Therapeutics | ||||
Collaborators ICMJE | Bristol-Myers Squibb | ||||
Investigators ICMJE |
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PRS Account | Nektar Therapeutics | ||||
Verification Date | January 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |