Immunogen announced the U.S. FDA has recommended the Company conduct a new Phase 3 randomized trial to evaluate the safety and efficacy of mirvetuximab soravtansine in patients with high folate receptor alpha (FRα)-positive, platinum-resistant ovarian cancer as part of a Type C meeting held this week.
ImmunoGen requested the meeting to discuss the results of the Phase 3 FORWARD I trial and a potential path to registration for mirvetuximab monotherapy. The agency advised because FORWARD I did not meet its primary endpoint under the pre-specified statistical analysis plan, the data generated assessing the secondary endpoints from the study could not be used to support an application for accelerated approval. The FDA provided guidance regarding the design and endpoints of a potential registration study. ImmunoGen is exploring all potential pathways toward continuing the development of mirvetuximab.
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 FRα 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 FRα expression. Immunogen presented results from the FORWARD 1 trial in March, showing the mirvetuximab soravtansine failed to increase PFS compared to chemotherapy in either study population.
About folate receptor alpha (FRα)-positive, platinum-resistant ovarian cancer
Ovarian cancer is a type of cancer that begins in the ovaries. Ovarian cancer often goes undetected until it has spread within the pelvis and abdomen. At this late stage, ovarian cancer is more difficult to treat and is frequently fatal. In ovarian cancer, FRα is overexpressed in 80% of epithelial ovarian cancers (EOCs) and expression has been shown to significantly correlate with histological grade and stage [10, 14]. The expression of FRα is considered a marker of tumor aggressiveness, and although there is conflicting data when all ovarian carcinoma histotypes are considered, elevated FRα expression is associated with lower disease-free interval (DFI) and poor overall survival (OS) in patients.
About mirvetuximab soravtansine
Mirvetuximab soravtansine is a humanized FRα-binding antibody that targets the antibody-drug conjugate (ADC) specifically to FRα-expressing cancer cells with a chemotherapy agent, DM4. An ADC is an antibody for a specific cancer marker—in this case FRα—molecularly linked to a chemotherapy drug, in this case DM4.