718MO - Mirvetuximab soravtansine (MIRV) in recurrent platinum-sensitive ovarian cancer (PSOC) with high folate receptor-alpha (FRα) expression: Results from the PICCOLO trial

Background

MIRV is an antibody-drug conjugate comprising an FRα-binding antibody, cleavable linker, and maytansinoid DM4 payload, a potent tubulin-targeting agent and is FDA approved in patients with platinum-resistant ovarian cancer who received 1-3 prior treatment regimens. PICCOLO is a single-arm Phase 2 study evaluating the efficacy and safety of MIRV in patients with PSOC, primary peritoneal, or fallopian tube cancer.

Methods

PICCOLO enrolled PSOC patients with high (≥ 75% of cells with PS2+ staining intensity) FRα expression by immunohistochemistry (VENTANA FOLR1 [FOLR1-2.1] RxDx Assay) with at least 2 prior lines of platinum-containing therapy or documented platinum allergy. Patients received MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by the investigator; key secondary endpoint was duration of response (DOR); additional secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS).

Results

With a data cutoff of 17 Jan 2024, 79 patients were enrolled. 97.5% had prior taxanes, 81% prior poly (ADP-ribose) polymerase inhibitors (PARPi) [74.7% of whom progressed while on PARPi], 64.6% prior bevacizumab, 98.8% had 2+ prior lines of therapy, and BRCA status was 27.8% positive, 72.2% negative. ORR was 51.9% (95% CI 40.4, 63.3), including 6 complete and 35 partial responses. The mDOR was 8.3 months (95% CI 5.5, 10.8), mPFS was 6.9 months (95% CI 5.9, 9.6); OS was not mature at data cutoff. The most common treatment-emergent adverse events (TEAEs) (all grade and grade ≥ 3) were blurred vision (63% and 10%), dry eye (37% and 3%), nausea (37% and 1%), keratopathy (33% and 4%), and diarrhea (30% and 3%). TEAEs led to dose delays, reductions, and discontinuations in 61%, 42%, and 16% of patients, respectively.

Conclusions

MIRV demonstrated clinically meaningful antitumor activity and favorable tolerability in patients with FRα-high PSOC. The efficacy and safety data support the use of MIRV in PSOC patients with ≥ 2 prior platinum-containing regimens or platinum allergy. Clinical Trial: NCT05041257.

Clinical trial identification

NCT05041257.

Editorial acknowledgement

Legal entity responsible for the study

ImmunoGen, Inc.

Funding

ImmunoGen, Inc.

Disclosure

I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, Sutro, BMS, Adaptimmune, Daiichi Sankyo, ImmunoGen, Seagen, PMV Pharma; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: GINECO. All other authors have declared no conflicts of interest.