As reported in the Journal of Clinical Oncology by Ursula A. Matulonis, MD, of the Dana-Farber Cancer Institute, and colleagues, the phase II SORAYA study has shown activity of mirvetuximab soravtansine-gynx, an antibody-drug conjugate targeting folate receptor α (FRα), in women with platinum-resistant ovarian cancer with high FRα expression.1
The study supported the November 2022 accelerated approval of the agent for treatment of patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatments.
Ursula A. Matulonis, MD
In the study, 106 patients from sites in 11 countries were enrolled between June 2020 and May 2021 and received mirvetuximab soravtansine at 6 mg/kg every 3 weeks until progressive disease or unacceptable toxicity. Patients had to have received at least one and up to three prior therapies, including bevacizumab. A total of 51% of patients had received three prior lines of therapy, and 48% had received prior poly (ADP-ribose) polymerase (PARP) inhibitor treatment. The primary endpoint was investigator-assessed confirmed objective response rate.
At data cutoff (in April 2022), the median follow-up was 13.4 months. Among 105 patients evaluable for response, an objective response was observed in 34 patients (32.4%, 95% confidence interval [CI] = 23.6%–42.2%), including a complete response in 5 (4.8%). An additional 48 patients (45.7%) had stable disease. The disease control rate (including objective responses and stable disease of at least 12 weeks) was 51.4%. A total of 75 patients (71.4%) exhibited tumor reduction. Median time to response was 1.5 months (range = 1.0–5.6 months), generally coinciding with the first post-baseline scan. Median duration of response was 6.9 months (95% CI = 5.6–9.7 months). Median progression-free survival was 4.3 months (95% CI = 3.7–5.2 months). Median overall survival was 13.8 months (95% CI = 12.0 months to not reached), with 46% of events reported.
In subgroup analyses, objective response rates were 35.3% (95% CI = 22.4%–49.9%) among patients with one or two prior lines of therapy and 30.2% (95% CI = 18.3%–44.3%) among those with three prior lines. Median response durations were 5.9 months (95% CI = 4.2–9.6 months) and 7.4 months (95% CI = 3.5–10.7 months), respectively. Objective response rates were 38.0% (95% CI = 24.7%–52.8%) among patients with prior PARP inhibitor treatment and 27.5% (95% CI = 15.9%–41.7%) among those without prior PARP inhibitor treatment. Median response durations were 5.7 months (95% CI = 3.5–9.6 months) and 6.4 months (95% CI = 3.0 months to not reached), respectively.
Among 96 patients assessed by blinded independent review committee, an objective response was observed in 29 patients (30.2%, 95% CI = 21.3%–40.4%), with a complete response in 6 (6.3%). Stable disease was observed in an additional 54 patients (56.3%). Median time to response was 1.4 months (range = 1.0–5.4 months). Median response duration was not reached (95% CI = 5.0 months to not reached). Median progression-free survival was 5.5 months (95% CI = 3.8–6.9 months).
Among 106 patients in the safety population, the most common treatment-related adverse events of any grade were blurred vision (41%), keratopathy (29%), nausea (29%), and dry eye (25%). Treatment-related grade 3 or 4 adverse events occurred in 29% of patients (grade 4 in 1%), the most common being keratopathy (9%) and blurred vision (6%). Treatment-related peripheral neuropathy occurred in 18% of patients (all grade 1 or 2). Serious treatment-related adverse events occurred in 11% of patients. Treatment-related adverse events led to dose delay, dose reduction, and treatment discontinuation in 33%, 20%, and 9% of patients, respectively. Causes of treatment discontinuation included thrombocytopenia, keratopathy, fatigue, infusion-related reaction, sensory neuropathy, and respiratory failure.
Overall, 55 patients (52%) had any-grade blurred vision or keratopathy, with median time to onset of 1.3 months or 1.5 months, respectively. Dose reduction was required in 12 patients and treatment discontinuation, in 1. At data cutoff, 96% of grade ≥ 2 ocular events (blurred vision and keratopathy) had resolved to grade 0 or 1.
The investigators concluded: “[Mirvetuximab soravtansine] demonstrated consistent clinically meaningful antitumor activity and favorable tolerability and safety in patients with FRα-high [platinum-resistant ovarian cancer] who had received up to three prior therapies, including bevacizumab, representing an important advance for this biomarker-selected population.”
DISCLOSURE: The study was funded by ImmunoGen, Inc. Dr. Matulonis has received honoraria from Advaxis, Alkermes, and Symphogen; has had a consulting or advisory role with Merck, Novartis, NextCure, AstraZeneca, Blueprint Medicines, Trillium Therapeutics, GlaxoSmithKline, Agenus, 2X Oncology, Boehringer Ingelheim, and ImmunoGen; has received research funding from Merck, Novartis, Tesaro, Syndax, ImmunoGen, Mersana, Leap Therapeutics, Fujifilm, and SQZ Biotech; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca.
1. Matulonis UA, Lorusso D, Oaknin A, et al: Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: Results from the SORAYA study. J Clin Oncol. January 30, 2023 (early release online).