Mirvetuximab soravtansine, a folate receptor-targeting antibody-drug conjugate, in combination with bevacizumab, demonstrated impressive anti-cancer activity in the phase 1b FORWARD II trial.

 Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor α (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. Prior research showed that MIRV has encouraging anti-tumor activity in platinum-resistant ovarian cancer, either as monotherapy or in combination with bevacizumab [1,2]. As part of the phase 1b FORWARD II trial (NCT02606305), the combination of MIRV with bevacizumab was evaluated in patients with FRα-positive, platinum-agnostic ovarian cancer. This was defined as patients who had medium/high expression of FRα (≥50%/≥75% of cells with PS2+ staining intensity) and who were either platinum-resistant or platinum-sensitive.

In total, 60 patients were enrolled in the study (32 platinum-resistant, 28 platinum-sensitive). Patients received MIRV (6 mg/kg) and bevacizumab (15 mg/kg) on day 1 of a 21-day cycle. Prof. David O’Malley (Ohio State University, USA) presented the results of the study. At a median follow-up of 17.5 months, objective response rate in the total population was 50%; 33% in patients with medium FRα expression and 64% in patients with high FRα expression. Objective response rate was 59% in patients who were platinum-resistant (and had high FRα expression) and 69% in patients who were platinum-sensitive (and had high FRα expression). Median duration of response was 9.7 months in the total population and 11.8 months in the patients with high FRα expression (12.7 months in the platinum-sensitive patients and 9.4 months in the platinum-resistant patients of those with high FRα expression).

Of patients who had high FRα expression, 32/33 (99%) showed a deep and rapid anti-tumor response regardless of platinum status. The most common treatment-related adverse events were diarrhea (62%), blurred vision (60%), fatigue (60%), and nausea (57%). The most common treatment-related grade 3/4 adverse events were hypertension (17%) and neutropenia (13%). “The combination of MIRV with bevacizumab demonstrates impressive anti-tumor activity with durable responses and favorable tolerability in high FRα recurrent ovarian cancer,” concluded Prof. O’Malley. “These results suggest that MIRV has the potential to be a preferred partner for bevacizumab in patients with high FRα recurrent ovarian cancer regardless of platinum sensitivity and warrants further development of this combination.”

  1. Moore K, Ann Oncol 2019; 30 (suppl 5): V403.
  2. O’Malley DM, et al. Gyn Oncol 2020; 157: 379-385.
  3. O’Malley DM, 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. ASCO 2021 Virtual Meeting, abstract 5504.

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