“Even though FORWARD I did not meet its primary endpoint, I continue to be impressed with the efficacy and tolerability of mirvetuximab soravtansine in ovarian cancer patients, especially in the subset with high FRa expression,” said Dr. Kathleen Moore, Associate Director of Clinical Research at the Stephenson Cancer Center at the University of Oklahoma. “I look forward to continuing to work with ImmunoGen to analyze the Phase 3 data and determine the most appropriate path to bringing mirvetuximab soravtansine to those patients who benefit most from it.”
The FORWARD I Phase 3 trial randomized 366 patients 2:1 to receive either mirvetuximab soravtansine or the physician's choice of single-agent chemotherapy (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel). Eligibility criteria included patients with platinum-resistant ovarian cancer that expressed medium or high levels of FRa who have been treated with up to three prior regimens. The primary endpoint of this study was PFS, which was assessed using the Hochberg procedure in the entire study population and in the subset of patients with high FRa expression. The Hochberg procedure enables the simultaneous testing of two overlapping populations. Under this statistical analysis plan, if the p-value of the primary endpoint in either population is greater than 0.05, the p-value in the other population needs to be less than or equal to 0.025 to achieve statistical significance.
“Based upon the efficacy signals we observed in the high FRa subset with PFS, confirmed overall response rate and overall survival, we are conducting additional analyses to further evaluate the potential benefit of mirvetuximab soravtansine for FRa-positive platinum-resistant ovarian cancer,” said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. “We want to thank the patients who participated in this trial, the clinical investigators, and the support staff for their hard work, as we continue to pursue our goal of finding innovative cancer treatments for patients in need.”
Key findings from FORWARD I are as follows:
In the entire study population, the confirmed overall response rate was higher for mirvetuximab soravtansine than for chemotherapy (22% vs 12%, p-value 0.015), without a significant difference in the primary endpoint of PFS (HR 0.98, p-value 0.897) or overall survival (HR 0.81, p-value 0.248). In the pre-specified high FRa subgroup (218/366, 60%) PFS was longer in patients who received mirvetuximab soravtansine compared with chemotherapy (HR 0.69, p-value 0.049). Given that the p-value in the entire study population exceeded 0.05, the statistical analysis plan for the study required the p-value in the high subset to be less than or equal to 0.025 to achieve statistical significance. Confirmed overall response rate was higher for mirvetuximab soravtansine than for chemotherapy (24% vs 10%, p-value 0.014). Overall survival was longer in patients who received mirvetuximab soravtansine compared with chemotherapy (HR 0.62, p-value 0.033). Mirvetuximab soravtansine was well-tolerated, with fewer patients experiencing grade 3 or greater adverse events (46% vs 61%), fewer dose reductions (20% vs 31%), and fewer discontinuations due to drug-related adverse events (5% vs 8%) compared with chemotherapy. The safety profile of mirvetuximab soravtansine was confirmed, with the most common adverse events including nausea (54% all grades; 2% grade 3 or greater), diarrhea (44% all grades; 4% grade 3 or greater), and blurred vision (43% all grades; 3% grade 3 or greater). “This study with mirvetuximab did not result in the outcome that we had hoped for in platinum-resistant patients. We will further assess the data from FORWARD I to determine potential next steps with a monotherapy approach. In parallel, we have generated encouraging data with mirvetuximab combination regimens and will evaluate our ongoing studies as an independent path forward to support a registration in ovarian cancer,” said Mark Enyedy, ImmunoGen’s President and Chief Executive Officer. “ImmunoGen is in a strong financial position with approximately $295 million in cash on our balance sheet, and we will continue to advance our portfolio of next-generation ADCs, which includes three additional development candidates targeting a range of tumor types in both hematologic malignancies and solid tumors.”
ImmunoGen intends to present additional results from FORWARD I at an upcoming medical meeting.
