Mirvetuximab soravtansine is an ADC comprised of a FRα-binding antibody linked to the tubulin-disrupting maytansinoid DM4. This agent activates monocytes and upregulates immunogenic cell death markers on ovarian tumor cells, providing a rationale for combining with immune checkpoint blockade. Mirvetuximab soravtansine is being evaluated in combination with pembrolizumab in patients with PROC.
Eligibility criteria include FRα positivity by IHC (≥ 25% of cells with ≥ 2+ staining intensity), 2-4 prior systemic treatments, and no prior immunotherapy. Mirvetuximab soravtansine (6 mg/kg; adjusted ideal body weight) and pembrolizumab (200 mg) were administered intravenously on day 1 of a 21-day cycle. Responses were assessed with RECIST 1.1 and adverse events (AEs) by CTCAE v4.03.
During dose-escalation (n = 14 patients), the mirvetuximab soravtansine-pembrolizumab combination demonstrated favorable tolerability, with primarily ≤ grade 2 AEs observed. Overall, the AE profile was manageable and consistent with the known profiles of each agent. In addition, promising evidence of durable antitumor activity was observed, including a confirmed objective response rate of 43%, median duration of response of 6.9 months, and median progression-free survival of 5.2 months. These findings supported enrollment of an expansion cohort to further evaluate this combination in the setting of PROC. At time of analysis, 37/46 patients were enrolled, who received a median of 3 prior regimens. Median age was 62y (range 40-77), and 92% had tumors with high grade serous histology. Initial safety, antitumor activity, and exploratory biomarker data will be presented, including for the subset of patients with medium/high FRα expression, which showed the highest degree of clinical activity during escalation.
Preliminary data have demonstrated a manageable safety profile and encouraging signals of clinical activity for the mirvetuximab soravtansine-pembrolizumab combination in recurrent PROC. The results of this expansion cohort will guide further development of this novel combination.
Clinical trial identification
Legal entity responsible for the study
U.A. Matulonis, K.N. Moore, L.P. Martin, M.J. Birrer, D.M. O’Malley: Advisory board: ImmunoGen, Inc. I.B. Vergote: Advisory board: ImmunoGen, Inc. K. Malek: Employee: ImmunoGen, Inc. All other authors have declared no conflicts of interest.