Phase 2 rinatabart sesutecan (Rina‑S) FRα-targeted antibody–drug conjugate with exatecan (topoisomerase I inhibitor)

Genmab’s Phase 2, open-label, multicohort study evaluates Rina‑S monotherapy in advanced/metastatic, progressive, unresectable gastrointestinal cancers after prior standard therapies, enrolling up to ~160 participants across multiple cohorts. Rina‑S is a folate receptor alpha (FRα)-directed monoclonal antibody–drug conjugate that delivers an exatecan payload, a topoisomerase I inhibitor that drives DNA damage during replication and can trigger tumor cell death. The design focuses on anti-tumor activity alongside safety/tolerability and pharmacokinetics/pharmacodynamics, with continued dosing permitted for participants who maintain disease control and tolerate treatment (21-day cycles). The key scientific/commercial angle is extending an FRα-directed ADC platform beyond gynecologic tumors into GI indications where FRα expression can be present but heterogeneous, potentially enabling a biomarker-enriched ADC strategy rather than histology-only development. For most advanced GI cancers today, care is sequential systemic therapy—fluoropyrimidine/platinum/irinotecan-based chemotherapy backbones, targeted agents when actionable alterations are present (e.g., HER2, FGFR2, BRAF, CLDN18.2), and immunotherapy primarily for MSI-high/dMMR or select biomarker-defined groups—so this tests whether an FRα-directed topo1 ADC can add a new single-agent option in later lines.