Phase 1 arginine supplementation metabolic immunomodulator with pembrolizumab PD-1 blockade in PROC

This open-label, non-randomized Phase 1 study tests whether supplemental L-arginine (oral and/or IV) can safely be added to common chemoimmunotherapy backbones for high-grade, platinum-resistant ovarian/fallopian tube/primary peritoneal cancer (PROC). It uses parallel cohorts stratified by PD-L1 CPS (CPS>1: physician choice of Cohort A or B; CPS<1: Cohort B only) and evaluates safety/PK plus early activity (ORR, DoR, DCR, PFS, OS). The investigational component is arginine repletion (metabolic substrate that can support T-cell function in immunosuppressive tumor microenvironments), layered onto Merck’s pembrolizumab (PD-1 monoclonal antibody) with Genentech/Roche’s bevacizumab (VEGF monoclonal antibody) and either paclitaxel (microtubule inhibitor; Cohort A) or low-dose oral cyclophosphamide (DNA-alkylating agent; Cohort B). Scientifically, it’s a pragmatic “metabolism + checkpoint” add-on that could be commercially relevant if a low-cost supportive agent measurably boosts IO responses in a setting where pembrolizumab benefits are inconsistent. Today’s care for platinum-resistant disease is sequential single-agent chemotherapy (weekly paclitaxel, PLD, topotecan, gemcitabine) ± bevacizumab, and folate receptor alpha–positive tumors may receive mirvetuximab soravtansine; this trial explores arginine as an adjunct to improve durability without changing the core regimen.