The Efficacy and Safety of Mirvetuximab Soravtansine in FR
Mené sur 79 patientes atteintes d'un cancer de l'ovaire FR alpha+ récidivant et sensible aux sels de platine, cet essai de phase 2 évalue l'efficacité, du point de vue du taux de réponse objective, de la durée de la réponse, de la survie sans progression et de la survie globale, et la toxicité d'un traitement de troisième ligne ou supérieure par mirvetuximab-soravtansine
Background : Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FR
α)-targeting antibody-drug conjugate with US Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase 2, global, open-label, single-arm trial of MIRV as third-line or greater (
≥3L) treatment in patients with FR
α-positive (
≥75% of cells with ≥2+ staining intensity) recurrent platinum-sensitive ovarian cancer (PSOC). Patients and methods : Participants received MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death. Primary endpoint was investigator-assessed objective response rate (ORR). Key secondary endpoint was investigator-assessed duration of response (DOR). Additional endpoints included investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Analyses of subgroups by disease characteristics (eg, platinum-free interval) and treatment history (eg, prior bevacizumab and poly [ADP-ribose] polymerase inhibitor [PARPi] treatment), were exploratory. Results : Seventy-nine participants were enrolled and efficacy evaluable. The primary endpoint was met; ORR was 51.9% (95% CI, 40.4-63.3). Median DOR was 8.25 months (95% CI, 5.55-10.78) and median PFS was 6.93 months (95% CI, 5.85-9.59). OS was not mature at data cutoff. ORR was 45.8% (95% CI, 32.7-59.2) in participants with PD while on/within 30 days of prior PARPi (n=59) and 60.0% (95% CI, 14.7-94.7) in those without PD with prior PARPi (n=5). No new safety signals occurred; most common treatment-emergent adverse events (TEAEs) were gastrointestinal, neurosensory, and resolvable ocular events. TEAEs led to discontinuation in 13 participants (16%) and death in 2 participants (3%). Conclusions : MIRV as ≥3L treatment in heavily pretreated recurrent FR
α-positive PSOC demonstrated notable efficacy and tolerable safety, including among those with prior PD on or within 30 days of PARPi. (Funding, ImmunoGen, Inc; NCT05041257).