Sofetabart Mipitecan Shows Activity Across FRα Expression Levels in PROC

Sofetabart mipitecan (Sofe-M), an investigational folate receptor α (FRα)–directed antibody-drug conjugate (ADC), yielded responses in heavily pretreated patients with high-grade ovarian cancer regardless of FRα expression, according to results from the first-in-human phase 1 trial (NCT06400472) published in Annals of Oncology.¹

What efficacy results were reported with Sofe-M?

Among 105 patients treated at 2, 3, 4, or 6 mg/kg every 21 days, the confirmed overall response rate (ORR) was 50.5% (95% CI, 40.5%-60.4%), including 5 complete responses and 48 partial responses. The disease control rate was 80.0% (95% CI, 71.1%-87.2%). By dose level, the ORR was 37.1% (95% CI, 21.5%-55.1%) at 2 mg/kg, 58.8% (95% CI, 32.9%-81.6%) at 3 mg/kg, 59.0% (95% CI, 42.1%-74.4%) at 4 mg/kg, and 50.0% (95% CI, 23.0%-77.0%) at 6 mg/kg. The authors ultimately selected 3 mg/kg as the recommended phase 3 dose.

The median progression-free survival (PFS) was 8.1 months (95% CI, 6.4-8.5) at a median follow-up of 12.9 months, and the median duration of response was 9.1 months (95% CI, 6.4-11.4). The median time to response was 2.1 months, and 19 of 53 responders remained on treatment at the March 5, 2026, data cutoff.

Did responses depend on FRα expression or prior mirvetuximab soravtansine?

The ORR was 44.4% (95% CI, 30.9%-58.6%) in patients with tumor FRα expression below 75% at 2+ or greater staining intensity and 56.5% (95% CI, 41.1%-71.1%) in those with expression of 75% or greater at 2+ or greater staining. Among 19 patients previously treated with mirvetuximab soravtansine-gynx (Elahere), the ORR was 57.9% (95% CI, 33.5%-79.7%). Two responders had minimal or no detectable FRα staining.

What was the safety profile of Sofe-M?

As of the data cutoff, the median time on treatment was 6.4 months. The most common any-grade treatment-emergent adverse effects (AEs) were nausea (64.8%), fatigue (56.2%), and anemia (47.6%). Grade 3 or higher treatment-related AEs occurred in 42.9% of patients overall, and in 35.3% at 3 mg/kg and 56.4% at 4 mg/kg. These were mostly hematologic, including grade 3 anemia (24.8%) and neutropenia (grade 3, 16.2%; grade 4, 7.6%).

No keratopathy or grade 3 or higher neuropathy was observed. Pneumonitis or interstitial lung disease occurred in 12 patients (11.4%), including 2 grade 3 events. Treatment-emergent AEs led to treatment discontinuation in 11 patients (10.5%).

“Sofe-M demonstrated durable clinical activity and a tolerable safety profile, notably absent of keratopathy and high-grade neuropathy, in heavily pre-treated patients with [platinum-resistant ovarian cancer], regardless of FRα expression level or prior treatment with [mirvetuximab soravtansine],” wrote lead study author Isabelle Ray-Coquard, MD, PhD, HDR, professor of medical oncology at Université Claude Bernard Lyon 1, medical oncologist at the Centre Léon Bérard, Lyon, and president of European Network of Gynaecological Oncological Trial Groups (ENGOT), and coauthors, in the study.¹

How was the phase 1 trial designed, and what is next?

The open-label, multicenter trial enrolled adults with histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube cancer and an ECOG performance status of 0 or 1, regardless of FRα expression. Patients had a median of 5 prior lines of systemic therapy (range, 1-11), and 98.1% had platinum-resistant disease. Sofe-M was administered intravenously every 3 weeks until confirmed disease progression, consent withdrawal, or unacceptable toxicity. Dose escalation evaluated 2, 4, and 6 mg/kg, with 3 mg/kg added as a backfill cohort, followed by a randomized dose-optimization cohort.

The FDA granted breakthrough therapy designation to Sofe-M for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer after prior bevacizumab (Avastin) and mirvetuximab, if eligible.² The registrational phase 3 FRAmework-01 trial (NCT07213804) is evaluating Sofe-M as monotherapy in platinum-resistant disease and with bevacizumab in platinum-sensitive disease.

References

1. Ray-Coquard I, O'Malley DM, Oaknin A, et al. Sofetabart mipitecan, an antibody drug conjugate targeting folate receptor alpha, in high grade ovarian cancer: results from the first-in-human phase 1 study. Ann Oncol. Published online 2026. doi:10.1016/j.annonc.2026.10.001
2. 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. Eli Lilly and Company. January 20, 2026. Accessed October 21, 2026. https://tinyurl.com/yeewxma2