This trial is designed to evaluate multiple clinical hypotheses and mechanistically-defined combinations to evaluate the safety and efficacy of first-line chemo-immunotherapy combinations in participants with metastatic pancreatic ductal adenocarcinoma (mPDAC).
This is an open-label, non-randomized, exploratory platform trial designed to assess the safety and antitumor activity of immunotherapy, in combination with standard of care chemotherapy, in participants with mPDAC who have not received prior therapy. Where supportive mechanistic data are available, immunotherapy may also be combined with other treatment modalities (eg, radiation). Each cohort of this platform trial will test a different immunotherapy combination and consist of up to 2 stages: an initial stage (Stage 1) to evaluate safety, biomarkers, and/or clinical activity of the combination and an expanded cohort (Stage 2), when warranted, based on the safety, clinical activity, and/or biomarker results from Stage 1. The Sponsor intends to modify and/or add new combinations to the protocol as data emerge from scientific findings, in this and other trials. This trial will be conducted in participants with histologically or cytologically documented diagnosis of mPDAC, with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, who have not received prior systemic therapy for their disease in the metastatic setting. Participants must have adequate organ and hematologic function and acceptable performance status. Participants must consent to tumor biopsies, including a pre-treatment (baseline) and on-treatment samples.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Nivolumab will be administered intravenously at 360 mg every 3 weeks for up to 2 years.
For Cohort A and B, ipilimumab will be administered intravenously at 1mg/kg every 6 weeks for up to 2 cycles. For Cohort C, ipilimumab will be administered intravenously at 1mg/kg on C2D1 and C4D1.
Hydroxychloroquine will be administered orally daily for up to 2 years.
University of California, Los Angeles
Los Angeles, California, United States
University of California, San Francisco
San Francisco, California, United States
Stanford University
Stanford, California, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Incidence and severity of adverse events
Time frame: Up to 2.5 years
Objective response rate (ORR)
Defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: Up to 2.5 years
Disease control rate (DCR)
Defined as the proportion of participants who achieve confirmed CR or PR or stable disease (SD) lasting at least 16 weeks
Time frame: At 9 months
Duration of response (DOR)
Defined as the time from first documentation of response (CR or PR) to first radiographic documentation of progressive disease (PD) or death due to any cause.
Time frame: Up to 2.5 years
Progression-free survival (PFS)
Defined as the time from initiation of study intervention to date of first documented radiographic progression of disease or death due to any cause.
Time frame: Up to 2.5 years
Overall survival (OS)
Defined as the time from initiation of study intervention until death due to any cause.
Time frame: Up to 2.5 years
Overall survival (OS) at 12 months
Defined as the time from initiation of study intervention until death due to any cause.
Time frame: At 12 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Nab-paclitaxel will be administered intravenously at 125 mg/m2 for 2 weeks on and 1 week off, for at least 24 weeks, unless treatment discontinuation criteria are met.
Gemcitabine will be administered intravenously at 1000 mg/m2 for 2 weeks on and 1 week off, for at least 24 weeks, unless treatment discontinuation criteria are met.
NG-350A will be administered intravenously on Cycle 1 Days 15 (1e12 viral particles), 17 (3e12 viral particles), and 19 (3e12 viral particles).
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States
M.D. Anderson Cancer Center
Houston, Texas, United States