SUMMARY: The FDA on November 14, 2022, granted accelerated approval to ELAHEREĀ® (mirvetuximab soravtansine-gynx) for adult patients with Folate Receptor alpha (FR alpha) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. The FDA also on the same day approved the VENTANA FOLR1 (FOLR-2.1) RxDx Assay (Ventana Medical Systems, Inc.), as a companion diagnostic device to select patients for the above indication.
It is estimated that in the United States, approximately 19,880 women will be diagnosed with ovarian cancer in 2022, and 12,810 women will die of the disease. Ovarian cancer ranks fifth in cancer deaths among women, and accounts for more deaths than any other cancer of the female reproductive system. Approximately 75% of the ovarian cancer patients are diagnosed with advanced disease. Approximately 85% of all ovarian cancers are epithelial in origin, and approximately 70% of all epithelial ovarian cancers are High-Grade Serous adenocarcinomas. Patients with newly diagnosed advanced ovarian cancer are often treated with platinum-based chemotherapy following primary surgical cytoreduction. Approximately 70% of these patients will relapse within the subsequent 3 years and are incurable, with a 5-year Overall Survival rate of about 20-30%. Treatment options for patients with platinum-resistant ovarian cancer are limited, and patients are often treated with single-agent chemotherapy, with an Overall Response Rate of between 4% and 13%, short duration of response, and significant toxicities.
Approximately 35-40% of ovarian cancer patients express high levels of Folate Receptor alpha, and this expression correlates with advanced stages of disease and more malignant phenotypes. There is limited expression of Folate Receptor alpha in normal tissues and is limited to the choroid plexus, proximal renal tubules, placenta, and endometrium. Testing for Folate Receptor alpha can be performed on fresh or archived tissue.
ELAHEREĀ® (mirvetuximab soravtansine-gynx) is a first-in-class Antibody Drug Conjugate (ADC), directed against FR alpha, a cell-surface protein highly expressed in ovarian cancer. It is comprised of a Folate Receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, which is a potent tubulin inhibitor, disrupting microtubule formation, and thereby designed to kill the targeted cancer cells. Microtubules are major components of the cytoskeleton that give shape and structure to cells. ELAHEREĀ® is the first FDA approved ADC for platinum-resistant disease.
The FDA approval was based on the pivotal SORAYA trial, which is a single-arm study in 106 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, whose tumors expressed high levels of Folate Receptor alpha, and who had been treated with 1-3 prior lines of systemic treatment regimens. All patients were required to have received prior treatment with AVASTINĀ® (Bevacizumab). Enrolled patientās tumors were positive for FR alpha expression as determined by the above-mentioned FDA approved assay. Patients were eligible for the study if at least 75% of cells had 2+ staining intensity or greater, based on immunohistochemistry-based scoring. Patients were excluded if they had corneal disorders, ocular conditions requiring ongoing treatment, more than Grade 1 peripheral neuropathy, or noninfectious interstitial lung disease. Patients received ELAHEREĀ® 6 mg/kg (based on adjusted ideal body weight) IV infusion every three weeks, until disease progression or unacceptable toxicity. Assessments were made for tumor response every six weeks for the first 36 weeks, and every 12 weeks thereafter. The Primary endpoint was investigator-assessed Overall Response Rate (ORR), and key Secondary endpoint was Duration of Response (DOR).
The confirmed ORR was 31.7% including five Complete Responses, and the median Duration of Response was 6.9 months. Response rates were consistently seen regardless of the number of prior therapies or the use of a prior PARP inhibitor. The most common adverse reactions including laboratory abnormalities, were vision impairment, keratopathy, fatigue, nausea, peripheral neuropathy, increase in ALT and AST and cytopenias. Product labeling includes a boxed warning for ocular toxicity. The authors reported that the ocular events were reversible and primarily included low-grade blurred vision and keratopathy, which were managed with protocol-defined dose modifications. Approximately 60% of patients with symptoms had resolution prior to their next cycle of treatment, and less than 1% of patients discontinued therapy due to an ocular event.
It was concluded that ELAHEREĀ® had impressive anti-tumor activity, durability of response, and overall tolerability, and may be a new therapeutic option for patients with Folate Receptor alpha-positive platinum-resistant ovarian cancer.
Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: Results from the SORAYA study. Matulonis UA, Lorusso D, Oaknin A, et al: 2022 SGO Annual Meeting on Womenās Cancer. Abstract 242. Presented March 19, 2022.
