Lilly posts 79% response in Sofe-M ovarian study

Eli Lilly (LLY) has reported new Phase 1 results showing that its investigational antibody-drug conjugate sofetabart mipitecan (Sofe-M), in combination with bevacizumab, achieved a confirmed objective response rate of 79.3% in platinum-sensitive ovarian cancer. The response analysis covered 29 women with measurable disease out of a 33-patient cohort, with 23 patients responding. The trial recorded a disease control rate of 100% in this platinum-sensitive setting.

Within the responding group, there were six complete responses and 17 partial responses. Median duration of response had not been reached at a median follow-up of 6.2 months, and median progression-free survival was also not reached after a median follow-up of 10.2 months at the July 6, 2026 data cutoff. These data are being presented at the European Society for Medical Oncology 2026 Congress in Madrid.

The Phase 1 study evaluated Sofe-M plus bevacizumab in 33 women with platinum-sensitive ovarian cancer, defined as disease that returns more than six months after platinum-based chemotherapy. Patients received Sofe-M at 4 mg/kg and bevacizumab at 15 mg/kg. Participants had been heavily pretreated, with a median of three prior systemic treatment regimens, ranging from one to six.

Prior therapy exposure was common: 67% of patients had previously received a poly (ADP-ribose) polymerase inhibitor and 70% had received bevacizumab. Clinical activity with the Sofe-M combination was observed across different folate receptor alpha expression levels and regardless of prior PARP inhibitor treatment. Disease control in the evaluable cohort was 100%, with responses reported as consistent across biomarker subgroups.

The safety profile of Sofe-M plus bevacizumab was described as consistent with the known profiles of the individual medicines, with no new safety signals detected in this Phase 1 cohort. The most common treatment-emergent adverse events were epistaxis and nausea, each occurring in 73% of patients, followed by anemia in 58%, neutropenia in 55% and fatigue in 52%.

Grade 3 or higher neutropenia was reported in 42% of patients, and Grade 3 or higher anemia occurred in 24%. Febrile neutropenia was observed in 3% of participants. Dose reductions were implemented in 42% of patients, and 6% discontinued treatment due to adverse events. Any-grade neuropathy occurred in 9% of patients, with no Grade 3 or higher neuropathy reported.

Sofe-M is an investigational folate receptor alpha-targeting antibody-drug conjugate composed of an Fc-silent, FRα-specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker. FRα is expressed in almost all ovarian cancers at higher levels than in normal tissue, enabling targeting of tumor cells.

Building on the Phase 1 findings, Lilly (LLY) is studying Sofe-M in the global Phase 3 FRAmework-01 program across both platinum-sensitive and platinum-resistant ovarian cancer. FRAmework-01 has three randomized, open-label parts with progression-free survival as the primary endpoint. Part A evaluates Sofe-M monotherapy in platinum-resistant disease, while Parts B and C test Sofe-M plus bevacizumab in platinum-sensitive disease, split by prior PARP inhibitor exposure.

In the Phase 3 program, Sofe-M is being dosed at 3 mg/kg, a level selected as the recommended Phase 3 dose based on monotherapy safety, efficacy and pharmacokinetic data. Monotherapy response rates were comparable at 4 mg/kg and 3 mg/kg, while higher-dose treatment was associated with more Grade 3 or higher treatment-related adverse events and more frequent dose reductions.