Phase III FORWARD study of mirvetuximab soravtansine did not meet its primary endpoint to treat (FR alfa)-positive, platinum-resistant ovarian cancer

ImmunoGen, Inc., announced that its Phase III FORWARD I trial evaluating the safety and efficacy of mirvetuximab soravtansine compared to chemotherapy in patients with folate receptor alpha (FR alfa)-positive, platinum-resistant ovarian cancer did not meet its primary endpoint of progression-free survival (PFS) in either the entire study population or in the pre-specified subset of patients with high FR alfa expression.

The FORWARD I Phase III 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 FR alfa 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 FR alfa 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.

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 FR alfa 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).