Phase 2 tovecimig DLL4×VEGF bispecific antibody plus FOLFIRI in second-line metastatic CRC.

This open-label Phase 2 investigator-sponsored study evaluates whether adding tovecimig—Compass Therapeutics’ DLL4- and VEGF-directed bispecific monoclonal antibody (dual angiogenesis / Notch-pathway modulation)—can improve outcomes when combined with standard FOLFIRI in patients with advanced/metastatic colorectal cancer after exactly one prior systemic line. Participants receive 28-day cycles with tovecimig on Days 1 and 15 followed by FOLFIRI: irinotecan (topoisomerase I inhibitor), leucovorin (folate analog that potentiates 5-FU), and 5-fluorouracil (thymidylate synthase inhibitor). The eligible population is second-line metastatic CRC with prior primary-tumor resection (either earlier-stage resection followed by metastatic relapse, or resection for complication in the metastatic setting). Washington University School of Medicine sponsors the trial, creating a pragmatic test of whether a DLL4×VEGF bispecific can deepen benefit on top of a widely used chemotherapy backbone. Today’s second-line care is selected based on biomarkers and prior exposure (e.g., FOLFIRI or FOLFOX with a VEGF inhibitor, EGFR antibodies for RAS/RAF–wild-type left-sided tumors, and later-line oral options like trifluridine/tipiracil or regorafenib), so this explores a targeted anti-angiogenic intensification strategy in a common post–first-line setting.