Sofetabart Mipitecan Hits 50% Response Rate in Platinum-Resistant Ovarian Cancer

Sofetabart mipitecan (LY4170156), an investigational folate receptor alpha (FRα)-targeted antibody-drug conjugate (ADC), elicited strong antitumor activity in patients with recurrent platinum-resistant high-grade serous ovarian cancer (HGSOC), according to findings from a first-in-human phase 1a study presented at the 2026 SGO Annual Meeting.¹

In the efficacy-evaluable cohort of 104 patients, the confirmed and unconfirmed ORR was 50%, with 4 complete responses and 48 partial responses. Of note the ADC elicited clinical activity regardless of IHC-determined FRα expression: patients with low expression (0%-24%) had an ORR of 40% (10/25 patients), while those with the highest expression (≥75%) achieved a 54% ORR (25/46 patients). The disease control rate was 78% overall.

Also of note, the investigators observed that clinical activity was maintained even in patients who were heavily pre-treated, including those who had received prior mirvetuximab soravtansine-gynx (Elahere). Responses were also durable with 73% (38/52 patients) of responding patients remaining on treatment as of the July 30, 2025, data cutoff.

“Sofetabart mipitecan showed promising clinical activity in heavily pre-treated patients across all FRα expression levels and regardless of prior mirvetuximab soravtansine-gynx treatment,” said presenting author Bhavana Pothuri, MD, Division of Gynecologic Oncology, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY. “Sofetabart mipitecan was well-tolerated in patients with HGSOC with no significant toxicities,” added Pothuri.

Safety Profile of Sofetabart Mipitecan

Pothuri highlighted that sofetabart mipitecan did not lead to some of the significant toxicities typically associated with other FRα-targeted ADCs. No keratopathy was reported and rates of peripheral neuropathy (grade 1/2, 3%) and alopecia (grade 1/2, 10%) remained low.

The most frequent treatment-emergent adverse events (TEAEs) across all doses included nausea in 64% (grade ≥3, 3%) of patients, fatigue in 53% (grade ≥3, 2%), anemia in 39% (grade ≥3, 25%), vomiting in 36% (grade ≥3, 2%), neutropenia in 34% (grade ≥3, 24%), and diarrhea in 33% (grade ≥3, 1%).

Grade 4 neutropenia occurred in 8% of patients, and 2% experienced febrile neutropenia, notably without the use of prophylactic GCSF. Interstitial lung disease was observed in 8% of patients, though these cases were primarily grade 1 or 2, with only 2% reaching grade 3.

Dose reductions due to TEAEs occurred in 26% of the total population, increasing to 64% in the highest dose (6 mg/kg) cohort.

Study Design and Patient Characteristics

The phase 1a study utilized a dose-escalation (2 mg/kg–6 mg/kg every 3 weeks) and dose-optimization design to determine the recommended phase 2 dose. The trial enrolled 105 patients with ovarian cancer, the vast majority having serous histology (92%), followed by endometrioid (3%), carcinosarcoma (1%), and other types (4%).

The median patient age was 63 years (range, 40-89). About two-thirds (65%) of patients were White, 15% were Asian, 2% were Black or African American (2%), and 18% did not have race information available. Nearly two-thirds (64%) of patients had an ECOG performance status (PS) of 1 and the remainder (36%) had an ECOG PS of 0.

The investigators reported that central testing showed that 51% of patients had FRα expression <75% (at 2+ and/or 3+ intensity), 44% had expression ≥75%, and 5% were pending.

The population evaluated was heavily pretreated, having received a median of 5 (range 1-11) prior systemic regimens. Nearly all (96%) patients were platinum-resistant. Prior bevacizumab (Avastin) had been received by 88% of patients, 66% had prior PARP inhibitors, and 17% had prior mirvetuximab soravtansine-gynx.

Next Steps With Sofetabart Mipitecan

Based on the same data presented at the SGO meeting, the FDA granted breakthrough therapy designation to sofetabart mipitecan for the treatment of patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have previously received bevacizumab and mirvetuximab soravtansine-gynx.

The ADC is currently being evaluated in the global phase 3 FRAmework-01 trial (NCT07213804), which is investigating sofetabart mipitecan as monotherapy for platinum-resistant ovarian cancer and in combination with bevacizumab for platinum-sensitive disease.²

REFERENCES

1. Pothuri B, Ray-Coquard I, Kyi C, et al. Updated results from the first-in-human phase 1 study of LY4170156, an antibody drug conjugate (ADC) targeting folate receptor alpha (FRα) in recurrent platinum resistant high-grade serous ovarian cancer (HGSOC). Presented at: 2026 SGO Annual Meeting; April 10-13, 2025; San Juan, Puerto Rico.

2. A Two-Part Phase 3 Study of Sofetabart Mipitecan (LY4170156) in Participants With Platinum-Resistant (Part A) and Platinum-Sensitive (Part B) Ovarian Cancer. ClinicalTrials.gov. NCT07213804. Updated March 20, 2026. Accessed April 13, 2026. https://clinicaltrials.gov/study/NCT07213804.