Integrated Ocular Safety Summary Of Mirvetuximab Soravtansine From Four Clinical Trials In Patients With Folate Receptor Alpha (Frα)-Positive Recurrent Ovarian Cancer

Antibody-drug conjugates (ADCs) are a class of drugs designed to provide targeted cancer therapy with limited damage to surrounding healthy cells.  Several ADCs have been associated with ocular adverse events (OAEs) of varying presentation and severity, involving the anterior segment. This study aims to characterize the ocular safety profile of single-agent mirvetuximab soravtansine (MIRV) in patients (pts) with FRα-positive recurrent ovarian cancer and to review the clinical presentation and management of corneal AEs. MIRV is an ADC that has demonstrated significant anti-tumor activity in this difficult-to-treat population in the single-arm study SORAYA to support accelerated approval by the FDA in November 2022.

This retrospective pooled analysis included patients enrolled across four clinical trials: phase 1 first-in-human study IMGN853-0401, pivotal SORAYA, phase 3 FORWARD I, and phase 3 trial MIRASOL. MIRASOL is the confirmatory, randomized, global phase 3 trial designed to support approval worldwide.

Analysis included 682 pts (median age 63 years) and included patients with low, medium, and high FRα expression (PS2+) by immunohistochemistry (VENTANA FOLR1 [FOLR1-2.1] RxDx Assay). All pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity.  All patients were instructed to use prophylactic prednisolone acetate 1% eye drops at each cycle and preservative-free artificial tears throughout therapy. Dose modifications were implemented by the treating oncologist in response to the severity of OAEs according to predefined dose modification criteria.  OAEs and management strategies, including MIRV dose modifications, are reported.

The most common treatment-related OAEs (all grade, grade 3+) included blurred vision (41%, 4%), keratopathy (27%, 4%), and dry eye (24%, 2%). Keratopathy generally presented as punctate epithelial or subepithelial microcyst-like changes. The median time to onset for the most common ocular treatment-emergent adverse events, blurred vision, and keratopathy was 5.9 weeks and 6.7 weeks, respectively.  Of the pts who experienced any OAE, 53% had complete resolution, and 38% had partial improvement at the last follow-up. Complete resolution occurred in 71% of pts with blurred vision and 66% of pts with keratopathy. No corneal ulcers or perforation have been reported; no OAE has been reported to have permanent sequelae.

MIRV-associated OAEs are primarily characterized by transient changes to the corneal epithelium that manifested with blurred vision and microcyst-like epithelial keratopathy. Corneal adverse events generally resolved with supportive ophthalmic medical care and, if needed, dose modification. The findings highlight the important role of ophthalmology in the collaborative care of patients undergoing therapy with MIRV.  By evaluating the severity of MIRV-associated ocular adverse events and communicating with the oncology care team, the ophthalmologist enables prompt intervention with dose modification to mitigate ocular adverse events and avoid unnecessary discontinuation of cancer therapy.