Phase 1 tepotinib + ivonescimab trial tests MET inhibitor plus PD-1×VEGF bispecific.

Memorial Sloan Kettering Cancer Center is running this Phase 1 pilot to establish a tolerable and preliminarily active combination of tepotinib (a small-molecule MET/c-Met/HGFR tyrosine kinase inhibitor; Merck KGaA/EMD Serono markets tepotinib as Tepmetko) with ivonescimab (a PD-1 and VEGF-targeted bispecific antibody, developed by Akeso). The study uses a standard 3+3 dose-finding design followed by a small dose-expansion, enrolling about 16 total patients with advanced or recurrent NSCLC (stage IIIB/C not amenable to local therapy, or stage IV) confirmed to harbor MET exon 14 skipping by an FDA-approved/CLIA-type assay. Patients may have received prior MET inhibitor therapy and/or prior immune checkpoint inhibitor therapy, but must not have received prior angiogenesis inhibitors (e.g., bevacizumab/ramucirumab), framing the commercial/scientific angle as “re-challenging” a MET-driven population with a dual immune/anti-VEGF biologic layered onto targeted therapy. Today’s care for METex14+ advanced NSCLC often starts with a MET TKI (tepotinib or capmatinib) and then transitions to platinum-based chemotherapy ± immunotherapy depending on prior exposure and fitness; this trial explores whether adding PD-1×VEGF blockade can deepen or extend benefit versus MET inhibition alone.