Sofetabart mipitecan, an antibody drug conjugate targeting folate receptor alpha, in high grade ovarian cancer: Results from the first-in-human phase 1 study.

Authors

I Ray-Coquard, D M O'Malley, A Oaknin, A Madariaga, N Lakhani, W McKean, A Perez-Fidalgo, M Okera, S Kitano, T Koyama, J S Frenel, G Curigliano, M R Khajawa, M Cheol Lim, D Lorusso, V Pilla Reddy, R M Speck, A M Gilligan, A M Szpurka, M Manvelyan, Y Wu, C Wang, E Avsar, C F Friedman, D Sachdeva, C Kyi, B Pothuri

Published in

Annals of oncology : official journal of the European Society for Medical Oncology. Oct 08, 2026. Epub Oct 08, 2026.

Abstract

Folate receptor alpha (FRα) is overexpressed in most high-grade ovarian cancers (HGOC), but use of the FRα-targeting drug mirvetuximab soravtansine-gynx (MIRV) is limited by expression-level restrictions and toxicity profile. Sofetabart mipitecan (Sofe-M) is a novel FRα-targeting antibody-drug conjugate designed to overcome these barriers. Here we report safety, efficacy, and pharmacokinetics from the first-in-human phase 1 study.
This multicenter, open-label, phase 1 trial evaluated Sofe-M in patients with HGOC, regardless of FRα expression level. Prior MIRV treatment was permitted.
One-hundred-five patients with HGOC, the majority of whom were platinum resistant, received Sofe-M at 2, 3, 4 or 6 mg/kg every 21 days. Median age was 63.0 years, median number of prior treatments was 5.0 (1-11), 19 (18.1%) patients had prior MIRV, and 54 (51.4%) had tumor FRα expression <75% at ≥2+ intensity. Overall response rate was 50.5% (95% CI 40.5, 60.4) for all patients, 58.8% (95% CI 32.9, 81.6) at 3 mg/kg, 44.4% (95% CI 30.9, 58.6) for FRα <75%, 56.5% (95% CI, 41.1, 71.1) for FRα ≥75%, and 57.9% (95% CI 33.5, 79.7) for patients with prior MIRV exposure. Median progression-free survival was 8.1 months (95% CI 6.4, 8.5) and median follow-up was 12.9 months (95% CI 10.6, 15.2). Most common treatment-emergent adverse events (TEAEs) were nausea (64.8%), fatigue (56.2%), and anemia (47.6%). No keratopathies or grade ≥3 neuropathy were observed. At 3 and 4 mg/kg, the rate of Grade ≥3 treatment-related TEAEs was 35.3% and 56.4%, respectively. Treatment discontinuation due to TEAEs occurred in 11 patients (10.5%).
Sofe-M demonstrated a favorable tolerability profile, notably absent of keratopathy and high-grade neuropathy, with durable clinical activity in heavily pretreated HGOC patients regardless of FRα expression level or prior MIRV. These data support 3 mg/kg as the recommended phase 3 dose and provide the basis for the FRAmework-01 trial.
Phase 1 (NCT06400472); FRAmework-01 (NCT07213804).

PMID:
42849725
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.