Eli Lilly Sofe-M, the investigational folate receptor alpha (FRα) antibody-drug conjugate sofetabart mipitecan from Eli Lilly and Company (NYSE: LLY), produced a 79% confirmed objective response rate and a 100% disease control rate when paired with bevacizumab in platinum-sensitive ovarian cancer (PSOC). Lilly announced the Phase 1 findings on October 24, 2026, from Indianapolis. The company said the data will be shared in an oral presentation at the European Society for Medical Oncology (ESMO) Annual Congress in Madrid, Spain.
A confirmed response rate of 79% or higher was seen in both PARP inhibitor (PARPi)-treated and PARPi-naïve patients, according to the release. Lilly also reported that activity was similar across FRα expression levels, and that clinical activity held up in patients with prior PARPi exposure, a group that typically has poor outcomes with platinum-based chemotherapy.
Jacob Van Naarden, Executive Vice President and President of Lilly Oncology, said the PSOC standard of care has stayed unchanged for a decade and “demands new treatment options.” He added that the Lilly Sofe-M results give the company confidence as it advances the molecule through the Phase 3 FRAmework-01 program.
How Lilly Sofe-M Targets FRα in Ovarian Cancer
FRα is expressed in almost all ovarian cancers, at much higher levels than in healthy tissue, which makes it a target that can help direct treatment to tumor cells. The Lilly Sofe-M design builds on that biology by pairing a tumor-seeking antibody with a cell-killing payload.
Sofe-M (LY4170156) combines an Fc-silent, FRα-specific humanized monoclonal antibody with exatecan, a topoisomerase I inhibitor, through a proprietary cleavable polysarcosine linker called PSARlink. The antibody binds FRα on the tumor cell surface and delivers exatecan into the cell to disrupt DNA replication. Lilly says the medicine was designed to target FRα across all expression levels with an improved therapeutic index.
Lilly states that Sofe-M has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration for platinum-resistant ovarian cancer (PROC). The molecule is also being evaluated in the Phase 3 FRAmework-01 program. Readers can review regulatory background on the FDA Breakthrough Therapy pathway and see more on Lilly’s oncology pipeline.
Lilly Sofe-M Phase 1 Efficacy Results in Platinum-Sensitive Ovarian Cancer
The Phase 1 study is evaluating Sofe-M plus bevacizumab in patients with advanced solid tumors. It includes a cohort of 33 women with PSOC who received Sofe-M at 4 mg/kg with bevacizumab at 15 mg/kg. These patients had received a median of three prior systemic regimens (range 1–6), including prior PARPi in 67% and prior bevacizumab in 70%.
As of the July 6, 2026 data cutoff, the confirmed objective response rate among 29 patients with measurable disease was 79.3% (23 of 29). That figure included 6 complete responses (20.7%) and 17 partial responses (58.6%), and the disease control rate was 100%. Median duration of response and median progression-free survival were not reached at median follow-ups of 6.2 and 10.2 months, respectively.
Chrisann Kyi, MD, a gynecologic medical oncologist at Memorial Sloan Kettering Cancer Center, said the responses were durable and that the rate in a PARPi-pretreated population exceeds what published platinum re-challenge studies have reported. The Lilly Sofe-M safety profile and low discontinuation rate, she noted, support further investigation. Lilly disclosed that Dr. Kyi has financial interests related to Eli Lilly and Company.
| Efficacy Measure | Phase 1 Result (PSOC cohort) |
|---|---|
| Patients in cohort | 33 |
| Patients with measurable disease | 29 |
| Confirmed objective response rate | 79.3% (23/29) |
| Complete responses | 6 (20.7%) |
| Partial responses | 17 (58.6%) |
| Disease control rate | 100% |
| Median duration of response | Not reached (median follow-up 6.2 months) |
| Median progression-free survival | Not reached (median follow-up 10.2 months) |
| Data cutoff | July 6, 2026 |
Lilly Sofe-M Safety Profile and Dose Selection
Lilly reported that Sofe-M plus bevacizumab showed a safety profile consistent with the known profiles of each medicine, with no new safety signals. The most common treatment-emergent adverse events (TEAEs) were epistaxis (73%), nausea (73%), anemia (58%), neutropenia (55%) and fatigue (52%).
The most common Grade 3 or higher events were neutropenia (42%) and anemia (24%). Febrile neutropenia occurred in 3% of patients, and G-CSF prophylaxis was not mandated. Any-grade neuropathy occurred in 9% of patients with no Grade 3 or higher events. Dose reductions occurred in 42% of patients, and 6% discontinued treatment because of an adverse event.
The Phase 1 study used 4 mg/kg, but the Lilly Sofe-M Phase 3 trial uses 3 mg/kg. Lilly explains that 3 mg/kg was chosen as the recommended Phase 3 dose after reviewing monotherapy safety, efficacy and pharmacokinetic data. Objective response rates were comparable at 59.0% (4 mg/kg) and 58.8% (3 mg/kg), while Grade 3 or higher treatment-related adverse events were 56.4% versus 35.3%, and dose reductions were 41.0% versus 23.5%.
| Safety Measure | Result |
|---|---|
| Epistaxis (any grade) | 73% |
| Nausea (any grade) | 73% |
| Anemia (any grade / Grade 3 or higher) | 58% / 24% |
| Neutropenia (any grade / Grade 3 or higher) | 55% / 42% |
| Fatigue (any grade) | 52% |
| Febrile neutropenia | 3% |
| Neuropathy (any grade) | 9% (no Grade 3 or higher) |
| Dose reductions | 42% |
| Discontinuation due to adverse event | 6% |
Lilly Sofe-M in the FRAmework-01 Phase 3 Program and the Unmet Need
FRAmework-01 (NCT07213804) is a Phase 3, randomized, open-label, three-part study in recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer. Part A tests Lilly Sofe-M as monotherapy in platinum-resistant disease. Part B tests Sofe-M plus bevacizumab in platinum-sensitive disease that progressed on or within six months of finishing a PARPi. Part C tests the same combination in PARPi-naïve platinum-sensitive disease.
The primary endpoint is progression-free survival, assessed by the investigator in Part A and by blinded independent central review in Parts B and C. Key secondary endpoints are overall survival, objective response rate, duration of response and safety. Lilly says enrollment is ongoing globally, with the first registrational dose in Q4 2025 for PROC and Q1 2026 for PSOC. The trial runs with ENGOT, the GOG Foundation and the Asia-Pacific Gynecologic Oncology Trials Group.
The need is substantial. Per the release, ovarian cancer is the sixth leading cause of cancer death among women in the United States, according to the American Cancer Society, and about 70% of patients experience recurrence after initial platinum response. For patients who recur after platinum chemotherapy and PARPi maintenance, published real-world data show a 41.9% objective response rate on platinum re-challenge. The earlier OCEANS trial did not include PARPi-treated patients, who now make up most recurrent PSOC cases.
Lilly also notes that roughly half of PSOC patients have HRD-positive tumors. Earlier Phase 1 work in platinum-resistant disease, published in Annals of Oncology, reported responses across all FRα expression levels, including in patients previously treated with mirvetuximab soravtansine.
Statements about Phase 3 outcomes, regulatory approval and commercialization are forward-looking. Lilly cautions that future results may differ from Phase 1 data and that no guarantee exists that Sofe-M will prove safe and effective or be approved.
| FRAmework-01 Detail | Information |
|---|---|
| Registry identifier | NCT07213804 |
| Design | Phase 3, randomized, open-label, three-part |
| Part A | Sofe-M monotherapy, platinum-resistant disease |
| Part B | Sofe-M + bevacizumab, platinum-sensitive, progressed on or within 6 months of PARPi |
| Part C | Sofe-M + bevacizumab, PARPi-naïve platinum-sensitive |
| Primary endpoint | Progression-free survival |
| Phase 3 dose | 3 mg/kg |
| Results timeline | Not disclosed |
| Drug Profile | Information |
|---|---|
| Name | Sofetabart mipitecan (Sofe-M; LY4170156) |
| Sponsor | Eli Lilly and Company (NYSE: LLY) |
| Target | Folate receptor alpha (FRα) |
| Payload / linker | Exatecan (topoisomerase I inhibitor) / PSARlink |
| Regulatory status | FDA Breakthrough Therapy Designation (PROC); investigational |
| Presentation venue | ESMO Annual Congress, Madrid, Spain (oral) |
| Presentation date and session | Not disclosed |
