Mirvetuximab Soravtansine Plus Bevacizumab in FRα-Overexpressing Advanced Epithelial Ovarian Cancer

Niraparib-Bevacizumab Combo Improves Clinical Outcomes in Recurrent Ovarian Cancer

By Susan Moench, PhD, PA-C

This study evaluated the combination of bevacizumab with an antibody drug conjugate targeted to the folate receptor alpha in the setting of epithelial ovarian cancer.

Early results from a single-arm phase 1b study conducted in patients with recurrent epithelial ovarian cancer showed promising efficacy and tolerability for the combination of bevacizumab with mirvetuximab soravtansine. These findings were presented during the ASCO20 Virtual Scientific Program.

Mirvetuximab soravtansine is an antibody-drug conjugate comprised of a folate receptor alpha (FRα)-targeting antibody attached via a cleavage linker to DM4, a maytansinoid that disrupts microtubule function. Folate receptor alpha (FRα) is a folate-binding protein that is overexpressed in several epithelial cancers, including epithelial ovarian cancer. This finding, as well as the low expression level and restricted distribution of FRα in normal tissues has engendered interest in FRα as a therapeutic target.

Researchers reported the initial safety and efficacy results for the combination of mirvetuximab soravtansine plus bevacizumab, which was 1 of 5 nonrandomized, open-label study arms evaluating mirvetuximab soravtansine in combination with other agents as part of the phase 1b portion of the FORWARD II trial (ClinicalTrials.gov Identifier: NCT02606305). FORWARD II includes women with advanced platinum agnostic, FRα-positive epithelial ovarian, primary fallopian tube, or peritoneal cancer.

In this study, platinum agnostic disease was defined with respect to the last administered platinum dose as either platinum-resistant disease or platinum-sensitive disease where a non-platinum-based doublet would be an appropriate option. FRα-positive disease was characterized by medium or high expression of FRα corresponding to at least 50% (medium) or 75% (high) of tumor cells staining at 2+ intensity. Primary outcome measures included safety and objective response rate (ORR).

Of the 60 patients enrolled in the mirvetuximab soravtansine plus bevacizumab study arm, the median age was 60 years and the median number of prior lines of systemic therapy was 2. Regarding platinum status, the platinum-free interval was 6 months or less (ie, platinum resistant) in 53% of patients and greater than 6 months (ie, platinum sensitive) in the remaining 46% of patients. Thirteen percent of patients in the platinum-sensitive group had a platinum-free interval of greater than 12 months.

Most treatment-emergent adverse events (AEs) were of low grade, diarrhea and blurred vision were the most commonly reported. Grade 3 or higher treatment-emergent AEs included hypertension (12%) and neutropenia (10%). In addition, grade 1 and 2 pneumonitis occurred in 3 (5%) and 1 (1.7%) patient(s), respectively, and 22% of patients discontinued treatment due to treatment-related AEs.

Regarding efficacy, the confirmed ORR was 47% for the overall group receiving the antibody-drug conjugate in combination with bevacizumab. Notably, a higher ORR of 64% was observed for the subgroup of 33 patients with a high FRα expression level, and ORR was 59% and 69% in those with platinum-resistant or platinum-sensitive disease, respectively, demonstrating that response was not driven by platinum status.

In their concluding remarks, the study authors noted that “the combination of [mirvetuximab soravtansine] with [bevacizumab] demonstrates an encouraging ORR with a favorable tolerability profile in [patients] with recurrent ovarian cancer regardless of platinum sensitivity, particularly in those with tumors that express high levels of FRα.”

This article was published by Cancer Therapy Advisor.

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