The Efficacy and Safety of Mirvetuximab Soravtansine in FRα-Positive, Third-Line and Later, Recurrent Platinum-Sensitive Ovarian Cancer: The Single-Arm Phase 2 PICCOLO Trial.

Background: Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-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 FRα-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 FRα-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).