FDA Grants BTD to Sofetabart Mipitecan for Platinum-Resistant Ovarian Cancer

The FDA has granted breakthrough therapy designation (BTD) to sofetabart mipitecan (LY4170156) for the treatment of patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have previously received bevacizumab (Avastin) and mirvetuximab soravtansine (Elahere), if eligible.¹

Sofetabart mipitecan is a novel folate receptor alpha (FRα) antibody-drug conjugate that uses proprietary linker technology and an exatecan payload. 

The BTD follows encouraging preliminary results from the phase 1a/b study (NCT06400472) presented at the 2025 American Society of Clinical Oncology (ASCO) Meeting in June, and updated data presented at the 2025 European Society of Medical Oncology (ESMO) Congress in October. Data showed responses at all dose levels and across all FRα expression levels.

A preliminary objective response rate (ORR) of 55% was observed at the potential recommended phase 2 dose (4 mg/kg). As of the data cutoff date of March 9, 2025, the phase 1 study enrolled 95 patients with high-grade serous ovarian cancer across 4 dose levels (2 to 6 mg/kg).²

The study population was heavily pretreated, with a median of 5 prior systemic lines (range, 1–10); notably, 15% of patients had previously received mirvetuximab soravtansine. FRα expression was distributed across the cohort; 51% of patients demonstrated <75% expression, 34% demonstrated ≥75% expression, and 16% were awaiting results. The primary objectives focused on safety, pharmacokinetics, and ORR.

Early efficacy signals were observed across all dose levels and FRα expression strata, including in patients previously resistant to mirvetuximab soravtansine. Among 58 evaluable patients—excluding 37 who remained on-study prior to their first assessment—the ORR was 45% (n=26/58), with a disease control rate of 74% (n=43/58).

The safety profile was manageable, with no maximum tolerated dose reached. The most frequent treatment-emergent adverse events included nausea (64%), anemia (40%), fatigue (32%), vomiting (32%), diarrhea (28%), and neutropenia (27%). Significantly, the agent demonstrated a differentiated safety profile from other FRα-targeted therapies, with no reports of treatment-emergent neuropathy or ocular toxicity to date.

Recently, sofetabart mipitecan advanced into the phase 3 FRAmework-01 study (NCT07213804). The FRAmework-01 study is a global trial investigating sofetabart mipitecan as a monotherapy in patients with platinum-resistant ovarian cancer and as a combination therapy with bevacizumab in patients with platinum-sensitive ovarian cancer.¹

“We are pleased the FDA has granted [BTD] for sofetabart mipitecan, reflected the significant unmet need in platinum-resistant ovarian cancer and the promising initial results shown in our [p]hase 1 study,” said Jacob Can Naarden, executive vice president and president of Lilly Oncology, in a news release. “Building on compelling results generated to date, we’ve initiated our [p]hase 3 FRAmework-01 trial with the goal of bringing a potential therapeutic option to patients with advanced ovarian cancer, across all levels of folate receptor expression.”

REFERENCES

1.Lilly’s sofetabart mipitecan receives U.S. FDA’s breakthrough therapy designation for the treatment of certain patients with platinum-resistant ovarian cancer. News release. Lilly. January 20, 2026. https://tinyurl.com/2vuepavh

2.Lilly presents first clinical data for its investigation, next-generation FRα targeting ADC in platinum-resistant ovarian cancer at the 2025 ASCO Annual Meeting. News release. Lilly. Published June 2, 2025. Accessed January 20, 2026. https://tinyurl.com/yey5354v