Patients with ovarian cancer who have high-to-medium expression of folate receptor alpha responded well overall to mirvetuximab soravtansine.
Charles Morris, MBChB, MRCP
Patients with ovarian cancer who have high-to-medium expression of folate receptor alpha (FR-alpha) via immunohistochemistry responded well overall to mirvetuximab soravtansine (IMGN853), a novel FR-alpha-targeting antibody drug conjugate (ADC), in a recent study.
The findings were reported at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics and come from an analysis of 20 patients with platinum-resistant ovarian cancer, according to a press release from ImmunoGen, Inc, manufacturer for the drug. Patients received mirvetuximab soravtansine, which is currently in phase I testing, and were separated into categories of having low, medium, or high amounts of FR-alpha expression.
"These early findings are highly encouraging as they underscore the potential of mirvetuximab soravtansine to make an important difference for patients with ovarian cancer," said Charles Morris, MBChB, MRCP, chief development officer for ImmunoGen, Inc, in a press release. "The data are from patients with heavily pretreated platinum-resistant ovarian cancer, which is a difficult disease to treat. We will be assessing mirvetuximab soravtansine as single-agent therapy for patients with pretreated FR-alpha-positive ovarian cancer in our FORWARD I trial, a study we intend to use for registration purposes."
According to a press release, the drug worked well in patients with high-to-medium expression of FR-alpha. Nine of the 10 patients involved in the study with high amounts of FR-alpha expression had an objective response (2 complete responses [CRs], 7 partial responses [PRs] by RECIST 1.1 criteria). Of the nine patients, six remained on the treatment for at least 24 weeks.
High FR-alpha expression was classified as >75%, medium as 50% to 74%, and low as 25% to 49%, according to the company press release. Enrollment in the study required that patients test positive for at least a low-level expression of FR-alpha.
In data reported thus far mirvetuximab soravtansine has demonstrated an approximately 50% overall response rate (ORR) in later stage platinum-resistant ovarian cancer, which compares to typical response rates of 15% to 20% for currently approved chemotherapeutic agents, said Morris in an interview withTargeted Oncology. In patients with high target expression, a 90% ORR has been reported (9/10 patients) for mirvetuximab soravtansine.
Outside the 10 patients with high FR-alpha expression, 6 more patients tested positive for medium FR-alpha expression. While all six did experience tumor regression, one patient had both tumor shrinkage and a new lesion formation. Another patient in the medium-FR-alpha expression group received mirvetuximab soravtansine for 6 months and did not have an objective response.
Four more patients in the study tested positive for low FR-alpha expression and none had an objective response, according to the press release. One of the four patients was still on the treatment upon study cut-off.
Morris said the targeted nature of mirvetuximab soravtansine lends an air of importance to the treatments development.
There is a significant need for new therapies for patients with ovarian cancer. Chemotherapy agents traditionally used are not targeted, and the targeted approach of mirvetuximab soravtansine provides an opportunity to make an important difference for these patients, including potentially improved efficacy or better tolerability profile, he said.
According to the press release, the most commonly reported adverse events (AEs) were grade 1 or 2 diarrhea, blurred vision, vomiting, fatigue, and nausea. These AEs were reported by less than 30% of patients.
According to Morris, ImmunoGen hopes to report mature data from a 46-patient cohort in this study in 2016, as well as data from the FORWARD I trial examining mirvetuximab soravtansine as a single-agent therapy later this year.
ImmunoGen plans to assess mirvetuximab soravtansine in the FORWARD I trial as a single-agent therapy for the treatment of ovarian cancer previously treated with three to four prior regimens, said Morris. Patients in this trial will need to have medium or high expression of the target FR-alpha to qualify for enrollment. This trial is expected to start in late 2015. ImmunoGen also plans to assess mirvetuximab soravtansine in earlier lines of therapy in another trial called. FORWARD II, which will assess the compound as a combination therapy. This trial is also expected to start in late 2015.
Mirvetuximab soravtansine is currently has an orphan drug designation for the treatment of ovarian cancer by the FDA in the United States and in the EU.2