The US Food and Drug Administration (FDA) 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, who have received prior bevacizumab and mirvetuximab soravtansine, if eligible.
Sofetabart mipitecan is a novel folate receptor alpha (FRα) antibody-drug conjugate (ADC) that uses proprietary linker technology and an exatecan payload.
Breakthrough Therapy designation aims to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).
The FDA Breakthrough Therapy designation is based on encouraging preliminary results from the Phase 1a/b study.
Lilly presented initial Phase 1 results at the 2025 ASCO Annual Meeting in June and updated data at the 2025 ESMO Congress in October, showing responses at all dose levels and across all FRα expression levels, including in patients who progressed on prior mirvetuximab soravtansine.
These initial data also indicate a promising tolerability profile with low rates of interstitial lung disease, peripheral neuropathy, and alopecia, and no significant ocular toxicity.
Sofetabart mipitecan recently advanced into the Phase 3 FRAmework-01 study (NCT07213804), a global trial investigating the treatment as a monotherapy in patients with platinum resistant ovarian cancer (PROC), and in combination with bevacizumab in patients with platinum-sensitive ovarian cancer (PSOC).
Lilly is conducting the FRAmework-01 study in partnership with the European Network for Gynaecological Oncological Trial groups (ENGOT – lead groups GINECO/NOGGO e.V.), the GOG Foundation (GOG), and the Asia-Pacific Gynecologic Oncology Trials Group (APGOT).
References
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2 Scaranti, Mariana et al. “Exploiting the folate receptor α in oncology.” Nature reviews. Clinical oncology vol. 17,6 (2020): 349-359. doi:10.1038/s41571-020-0339-5.
3 Kalli, Kimberly R et al. “Folate receptor alpha as a tumor target in epithelial ovarian cancer.” Gynecologic oncology vol. 108,3 (2008): 619-26. doi:10.1016/j.ygyno.2007.11.020.
4 Viricel W, et al. Cancer Res. 2023;83(suppl 7):1544.
