LY4170156 Exatecan-Linker FRα ADC Delivers 55% ORR in Late-Line Platinum-Resistant Ovarian Cancer

LY4170156 is an Fc-silent antibody–drug conjugate targeting folate-receptor-α, armed with an exatecan payload via a polysarcosine linker. In platinum resistant ovarian cancer, 35-40% of tumors have high FRα expression and at least 75% of tumor cells are positive for at least 2+ intensity. In the open-label, first-in-human phase 1a/b study (NCT06400472), 45 patients with advanced FRα-expressing solid tumors received 2-6 mg/kg IV Q3W. The efficacy-evaluable cohort included 13 high-grade serous ovarian cancer (PROC) patients, who had a median of five prior lines and 44% FRα expression of less than < 75%. Across all doses, the ORR was 38% (1 CR, 4 PR) and disease control 69%; however, at the promising 4–6 mg/kg levels the ORR rose to 55% (11/20 overall responders in dose-expansion data) with responses seen in mirvetuximab-pretreated and FRα-low tumors. Grade ≥3 toxicities were mainly anemia (24%), neutropenia (11%), and febrile neutropenia (7%); no ocular or pulmonary signals emerged and only two dose-limiting toxicities occurred. Compared to mirvetuximab soravtansine’s 42% ORR and ≥grade 3 TRAEs in 41% of patients in the MIRASOL phase 3 trial, LY4170156 demonstrates comparable or higher activity, a cleaner safety profile, and efficacy below the 75% FRα cutoff that limits current SOC eligibility.