Novel drug combination for recurrent ovarian cancer

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 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 mirvetuximab soravtansine has encouraging anti-tumour 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 mirvetuximab soravtansine 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. Enrolled were 60 patients (32 platinum-resistant and 28 platinum-sensitive). Patients received mirvetuximab soravtansine (6 mg/kg) and bevacizumab (15 mg/kg) on day 1 of a 21-day cycle. Prof. David O’Malley (Ohio State University, OH, USA) presented the results of the study [3].

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-tumour response regardless of platinum status.

The most common treatment-related adverse events were diarrhoea (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%).

1. Moore K, et al. 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. Abstract 5504, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August, 202129 February, 2024