FDA grants Breakthrough Therapy designation to Eli Lilly’s FRα-targeting ADC sofetabart mipitecan for platinum-resistant ovarian cancer, supported by promising Phase 1 efficacy and safety data
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Eli Lilly and Company has announced that the U.S. Food and Drug Administration has granted Breakthrough Therapy designation to sofetabart mipitecan (LY4170156) for the treatment of adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. The designation applies to patients who have previously received bevacizumab and mirvetuximab soravtansine, if eligible. The decision highlights the urgent unmet need in this hard-to-treat setting and the encouraging early clinical data generated so far. For platinum-resistant ovarian cancer, where outcomes remain poor and treatment choices are limited, the designation signals strong regulatory confidence in the potential of sofetabart mipitecan.
Jacob Van Naarden, executive vice president and president of Lilly Oncology, said the designation reflects both the significant unmet medical need and the promising initial results. He added that the company has already moved forward into late-stage development to accelerate access for patients.
About sofetabart mipitecan and its mechanism
Sofetabart mipitecan is a next-generation folate receptor alpha (FRα) antibody-drug conjugate. It consists of an Fc-silent, FRα-specific humanized monoclonal antibody linked to an exatecan payload, a potent topoisomerase I inhibitor. The drug uses Lilly’s proprietary cleavable polysarcosine linker technology (PSARlink™), designed to improve stability in circulation while enabling efficient payload release inside tumor cells.
FRα is a cell-surface glycoprotein encoded by the FOLR1 gene and plays a role in folate transport, which supports cell growth and division. It is overexpressed in several solid tumors, including ovarian cancer, making it an attractive therapeutic target. Sofetabart mipitecan was engineered to target FRα across all expression levels, with the goal of delivering a broader and more consistent therapeutic benefit.
Clinical Evidence
The FDA decision is based on preliminary results from an ongoing Phase 1a/b study (NCT06400472). Initial findings were presented at the 2025 ASCO Annual Meeting and later updated at the 2025 ESMO Congress. The data showed objective responses across all tested dose levels and across the full spectrum of FRα expression, including in patients who had progressed on prior mirvetuximab soravtansine. Among 58 efficacy-evaluable patients, the objective response rate was 45%, with a disease control rate of 74%. At the potential recommended Phase 2 dose of 4 mg/kg, the objective response rate was 55 percent.
Early safety data suggest a favorable tolerability profile. Low rates of interstitial lung disease, peripheral neuropathy, and alopecia were reported, along with no significant ocular toxicity. These features are particularly relevant in ovarian cancer, where cumulative toxicity often limits long-term treatment.
Commenting on the announcement, Bhavana Pothuri, professor of Obstetrics and Gynaecology and Medicine at NYU Grossman School of Medicine and director of the Clinical Trials Office at the Perlmutter Cancer Center, noted that platinum-resistant ovarian cancer remains one of the most challenging areas in gynaecologic oncology. She highlighted that the Breakthrough Therapy designation and the early data across all FRα expression levels point to the potential of sofetabart mipitecan as a meaningful new option for patients.
Ongoing Phase 3 development: FRAmework-01
Sofetabart mipitecan has now advanced into the global Phase 3 FRAmework-01 trial (NCT07213804). The study is evaluating the therapy as a monotherapy in patients with platinum-resistant ovarian cancer and in combination with bevacizumab in patients with platinum-sensitive ovarian cancer. The trial is being conducted in collaboration with major international cooperative groups, including ENGOT, the GOG Foundation, and the Asia-Pacific Gynecologic Oncology Trials Group, underscoring its global scope.
Ovarian cancer background
Ovarian cancer is the fifth leading cause of cancer-related death among women in the United States. Although most patients initially respond to platinum-based chemotherapy, around 70 percent eventually experience disease recurrence. When relapse occurs during or within six months of platinum therapy, the disease is classified as platinum-resistant, a stage associated with limited treatment options and poor prognosis.
Reference
Lilly’s sofetabart mipitecan receives U.S. FDA’s Breakthrough Therapy designation for the treatment of certain patients with platinum-resistant ovarian cancer, 20 January 2026, Lilly’s sofetabart mipitecan receives U.S. FDA’s Breakthrough Therapy designation for the treatment of certain patients with platinum-resistant ovarian cancer | Eli Lilly and Company
Lilly presents first clinical data for its investigational, next-generation FRα targeting ADC in platinum-resistant ovarian cancer at the 2025 ASCO Annual Meeting, 02 June 2025, Lilly presents first clinical data for its investigational, next-generation FRα targeting ADC in platinum-resistant ovarian cancer at the 2025 ASCO Annual Meeting | Eli Lilly and Company
A Study of LY4170156 in Participants with Selected Advanced Solid Tumors, ClinicalTrials.gov ID NCT06400472, https://clinicaltrials.gov/study/NCT06400472