Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-resistant ovarian cancer: Final findings from the FORWARD II study.

5520 Background: Mirvetuximab soravtansine is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of mirvetuximab soravtansine with bevacizumab (BEV) was evaluated in pts with FRα-positive, platinum-resistant ovarian cancer (recurrence within 6 months after last platinum). Methods: Pts received mirvetuximab soravtansine (6 mg/kg; adjusted ideal body weight) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. Responses were assessed according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.03. Results: In total, 66 pts received combination dosing at this level: 11 during escalation and 55 in expansion. The median age was 63 years, pts received a median of 3 prior lines of systemic therapy (range 1-8), and 62% had received prior therapy with BEV. The most common AEs were diarrhea (58%), nausea (50%), and blurred vision (48%), and were primarily low grade (≤ grade 2). Serious AEs were largely gastrointestinal in nature, with small intestinal obstruction the most frequent individual event (4 pts, 6%). Objective responses were seen in 27 pts for a confirmed overall response rate (ORR) of 41% (95% CI, 29, 54), median progression-free survival (mPFS) interval of 7.1 months (95% CI, 4.9, 9.5), and median duration of response (mDOR) of 8.6 months (95% CI, 4.9, 14.9). In a subset analysis of pts (n = 16) who were bevacizumab-naïve, had 1-2 prior therapies, and medium/high FRα levels (i.e., ≥ 50% of cells with at least moderate staining intensity) the ORR was 56% (95% CI, 30, 80), mPFS 9.9 months (95% CI, 4.1, 15.9), and mDOR 12 months (95% CI, 6.0, 14.9). Conclusions: The combination of mirvetuximab soravtansine with BEV exhibits favorable tolerability in pts with platinum-resistant ovarian cancer, characterized by a manageable side-effect profile. The encouraging efficacy compares favorably to reported outcomes for BEV and chemotherapy seen in similar patient populations. These data support continued exploration of the combination in ovarian cancer. Clinical trial information: NCT02606305.