Lilly's Sofetabart Mipitecan shows 79% cORR in platinum‑sensitive ovarian cancer
- Sofe‑M plus bevacizumab achieved a confirmed objective response rate of 79.3% (23/29) and a disease control rate of 100% in 29 evaluable platinum‑sensitive ovarian cancer patients.
- Responses were consistent across FRα expression levels and prior PARP inhibitor exposure, with median duration of response and median PFS not reached at 6.2 and 10.2 months median follow‑ups.
- Phase 1 dosing was 4 mg/kg; a 3 mg/kg RP3D was chosen for Phase 3 based on comparable ORR and lower Grade ≥3 TRAEs (56.4% at 4 mg/kg vs 35.3% at 3 mg/kg).
- FRAmework‑01 is a three‑part global Phase 3 program (Part A: monotherapy in PROC; Part B: Sofe‑M + bevacizumab in PSOC post‑PARPi; Part C: Sofe‑M + bevacizumab in PARPi‑naïve PSOC) run with ENGOT, GOG and APGOT.
Phase 1 clinical activity
In a cohort of 33 women with platinum‑sensitive ovarian cancer, 29 had measurable disease and received Sofe‑M (4 mg/kg) plus bevacizumab (15 mg/kg). The confirmed objective response rate (cORR) was 79.3% (23/29) comprising 6 complete responses (20.7%) and 17 partial responses (58.6%). Median prior systemic regimens were three (range 1–6); 67% had prior PARPi and 70% prior bevacizumab. Median duration of response and median progression‑free survival were not reached at median follow‑ups of 6.2 and 10.2 months, respectively.
Safety
The safety profile was consistent with known effects of each agent and no new safety signals were identified. Common any‑grade TEAEs included epistaxis (73%), nausea (73%), anemia (58%), neutropenia (55%) and fatigue (52%). The most frequent Grade ≥3 events were neutropenia (42%) and anemia (24%); febrile neutropenia occurred in 3%. Any‑grade neuropathy occurred in 9% with no Grade ≥3 neuropathy. Dose reductions occurred in 42% of patients and 6% discontinued for adverse events; G‑CSF prophylaxis was not mandated.
FRAmework‑01 Phase 3 program
FRAmework‑01 consists of three global Phase 3 parts: Part A tests Sofe‑M monotherapy in platinum‑resistant disease; Part B tests Sofe‑M plus bevacizumab in platinum‑sensitive disease that progressed on or within six months of completing a PARPi; Part C tests Sofe‑M plus bevacizumab in PARPi‑naïve platinum‑sensitive disease. The program is conducted with ENGOT, the GOG Foundation and APGOT; first registrational doses were scheduled in Q4 2025 for PROC and Q1 2026 for PSOC. The primary endpoint across parts is progression‑free survival.
Drug design and mechanism
Sofetabart mipitecan (Sofe‑M; LY4170156) is an Fc‑silent, FRα‑specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker. It targets folate receptor alpha, which is highly expressed in most ovarian cancers, to deliver the payload selectively into tumor cells.
Source: Lilly