Highlights from

ASCO 2021

American Society of Clinical Oncology annual meeting

Virtual 4-8 June 2021

Novel drug combination for recurrent ovarian cancer

Summary: 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-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 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, US) 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-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%). “The combination of MIRV with bevacizumab demonstrates impressive anti-tumour activity with durable responses and favourable 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, Oza A et al. FORWARD I (GOG 3011): A phase III study of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), versus chemotherapy in patients (pts) with platinum-resistant ovarian cancer (PROC). Ann Oncol 2019;30(suppl 5):V403 [abstract]
  2. O’Malley D M, Matulonis U A et al. Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gyn Oncol 2020;157:379-385 [full text] (subscription required)
  3. O’Malley D M 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, 4-8 June 2021

Top image: FatCamera

Article image: Ridofranz

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.