Results of the phase 1b FORWARD II trial show that the MIRV/bevacizumab combination demonstrates promising antitumor activity with durable responses and favorable tolerability in high FRα recurrent ovarian cancer.
The phase 1b FORWARD II trial (NCT02606305) evaluated the preliminary antitumor activity of the folate receptor alpha (FRα)–targeting antibody–drug conjugate, mirvetuximab soravtansine (MIRV), in combination with bevacizumab in patients with FRα-positive recurrent ovarian cancer. The results of the final analysis of this trial were reported at the 2021 American Society of Clinical Oncology Annual Meeting.
The study enrolled patients with recurrent ovarian cancer who had received up to 3 previous regimens and were diagnosed with FRα-positive disease (medium/high expression; ≥50%/≥75% of cells with PS2+ staining intensity, and for whom a nonplatinum-based doublet would be appropriate). Patients with platinum-resistant ovarian cancer (PROC) were defined as those with recurrence ≤6 months after their last platinum dose; whereas patients with platinum-sensitive ovarian cancer (PSOC) would have responded to the last platinum therapy and did not progress ≤6 months. Eligible patients received MIRV (6 mg/kg) and bevacizumab (15 mg/kg) on day 1 of a 21-day cycle. The objective response rate (ORR), median duration of response (mDOR), and median progression-free survival (mPFS) were assessed.
A total of 60 patients received the MIRV/bevacizumab combination. The median age of the study population was 60 years. All participants had received a median of 2 previous lines of systemic therapy. The majority of patients showed high FRα expression (55%) and had PROC disease (53%). All patients had previous exposure to platinum compounds; 53% had a platinum-free interval (PFI) of ≤6 months, and 33% had a PFI of >6 to ≤12 months.
At a median follow-up of 17.5 months, a confirmed ORR of 47% was achieved in the overall population; mDOR was 9.7 months; and mPFS was 8.3 months. Higher responses were achieved in patients with high FRα expression (n = 33), with an ORR of 64%, mDOR of 11.8 months, and mPFS of 10.6 months. Among patients with PROC and high FRα expression (n = 17), ORR was 59%, mDOR was 9.4 months, and mPFS was 10.1 months. Among patients with PSOC and high FRα expression (n = 16), ORR was 69%, mDOR was 12.9 months, and mPFS was 13.3 months
Most adverse events were low grade, and the most frequent of any-grade treatment-related adverse events (TRAEs) were gastrointestinal and ocular in nature, including diarrhea (62%), blurred vision (60%), fatigue (60%), and nausea (57%). The most frequent grade 3/4 TRAEs were hypertension (17%) and neutropenia (13%); all other grade ≥3 events occurred in ≤10% of patients.
Based on these results, the investigators concluded that the MIRV/bevacizumab combination demonstrates promising antitumor activity with a durable response and favorable tolerability in high FRα recurrent ovarian cancer.
Source: MO’Malley D, Oaknin A, Matulonis UA, et al. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer: final analysis. J Clin Oncol. 2021;39(suppl_15). Abstract 5504.