Abstract 3482: Correlative analysis of metformin and nivolumab combination in treatment-refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC)
Abstract
Background: Preclinical results indicate that metformin can modulate immune cell populations in the tumor microenvironment of solid tumors by diminishing exhaustion of CD8+ tumor infiltrating cells and improving T cell responses. Studies also suggest that metformin could complement PD-1 blockade and potentiate its antitumor activity. Previously we reported the results of a phase II trial with metformin and nivolumab and here we report the findings of correlative analysis of the prospectively collected research samples of 18 patients.
Methods: We conducted a phase II trial with nivolumab and metformin in treatment-refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Nivolumab 480 mg IV every 4 weeks and metformin 1000 mg orally twice daily was administered in 28-day cycles following a 14-day metformin only lead-in phase. The primary endpoint was overall response rate (ORR). Secondary endpoints were overall survival (OS) and progression free survival (PFS). Pre-treatment and on-treatment research biopsies and correlative peripheral blood specimens were collected. Paired biopsies obtained at baseline and following treatment with metformin only (n=9) or metformin and nivolumab (n=9) and were stained with a panel of 13 markers using ChipCytometry technology by Canopy Biosciences. Sample was assessed prior to establishing the multiplex assay. 30 out of 36 samples were imaged and analyzed up to 30 Fields of View. Single cell recognition and quantitative…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 18 participants or records.
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