Phase 1b/2 TUB-040 NaPi2b-targeted topoisomerase I inhibitor (exatecan) ADC + Carbo/Bev

This multicenter Phase 1b/2 study evaluates TUB-040 (Tubulis GmbH)—a NaPi2b-directed antibody–drug conjugate delivering the topoisomerase I inhibitor payload exatecan via a cleavable linker—combined with carboplatin (a platinum DNA-damaging agent) and bevacizumab (Genentech/Roche’s VEGF-targeting monoclonal antibody) in recurrent, platinum-sensitive high-grade serous or endometrioid ovarian/fallopian tube/primary peritoneal cancer. The Phase 1b portion uses dose escalation to define the appropriate TUB-040 combination dose and determine the maximum tolerated dose while characterizing safety, tolerability, and pharmacokinetics; Phase 2 adds preliminary anti-tumor activity readouts. NaPi2b is a tumor-associated surface antigen with high prevalence in ovarian cancer, making it an enabling target for ADC delivery rather than requiring a rare biomarker-defined subgroup. Commercially, the key angle is moving a NaPi2b topo1i ADC into combination with a widely used platinum + anti-VEGF backbone to potentially extend benefit in platinum-sensitive relapse. Today’s care for platinum-sensitive recurrent ovarian cancer is typically platinum-based doublet chemotherapy (often carboplatin-based) with bevacizumab in appropriate patients, followed by maintenance (PARP inhibitor and/or bevacizumab depending on BRCA/HRD status, prior PARP exposure, and tolerability), and this trial explores whether adding targeted topo1i payload delivery can deepen responses without unacceptable overlapping toxicity.