Mirvetuximab soravtansine-gynx is a first-in-class antibody–drug conjugate comprising a FRα-binding antibody, cleavable linker and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.
The approval was based on objective response rate (ORR) and duration of response (DOR) data from the pivotal SORAYA (Study of Mirvetuximab Soravtansine in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression) trial (ClinicalTrials.gov Identifier: NCT04296890).
SORAYA was a single-arm study in 106 patients with platinum-resistant ovarian cancer whose tumors expressed high levels of FRα and who had been treated with one to three prior systemic treatment regimens—at least one of which included bevacizumab. The primary end point was confirmed ORR as assessed by the investigators and the key secondary end point was DOR.
Mirvetuximab soravtansine-gynx demonstrated an ORR of 31.7% (95% CI, 22.9%-41.6%), including five complete responses. The median DOR was 6.9 months (95% CI, 5.6-9.7 months), as assessed by the investigators.
The safety of mirvetuximab soravtansine-gynx has been evaluated in a pooled analysis from three studies among a total of 464 patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of mirvetuximab soravtansine-gynx (6 mg/kg adjusted ideal body weight administered intravenously once every three weeks).
The prescribing information for mirvetuximab soravtansine-gynx includes a boxed warning for ocular toxicity, including visual impairment, keratopathy, dry eye, photophobia, eye pain and uveitis. The most common adverse reactions (≥20% of patients), including laboratory abnormalities, were vision impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils and decreased hemoglobin.
MIRASOL, the confirmatory randomized trial designed to convert the accelerated approval of mirvetuximab soravtansine-gynx to full approval, is fully enrolled and top-line data are expected in early 2023. During the Biologics License Application review, FDA requested ImmunoGen submit preliminary ORR and DOR data from both arms of MIRASOL. To maintain data integrity for the ongoing MIRASOL trial, an independent third-party statistician performed the analyses and submitted the outputs directly to the FDA.
The FDA also granted approval of the Ventana FOLR1 (FOLR1-2.1) RxDx Assay, the only companion diagnostic to aid in identifying patients eligible for treatment with mirvetuximab soravtansine-gynx, developed by Roche.
Approximately 35% to 40% of patients with ovarian cancer express high levels of FRα, which is defined as greater than or equal to 75% tumor cells staining with 2+ intensity. Testing can be done on fresh or archived tissue; newly diagnosed patients can test at diagnosis to determine whether mirvetuximab soravtansine-gynx will be an option for them at the time of progression to platinum resistance. Testing is now available in the United States through four centralized laboratories and is expected to expand to additional laboratories over time.
“Platinum-resistant ovarian cancer is a notoriously challenging disease to treat. Given there have been no new therapies approved by FDA for this indication since 2014, Elahere’s accelerated approval is a tremendous advance in the ovarian cancer treatment paradigm,” said Anna Berkenblit, MD, the senior vice president and chief medical officer of ImmunoGen.
—Clinical Oncology News Staff