Abstract
A FRα-targeting antibody–drug conjugate induces responses in patients with platinum-resistant tumors.
Major finding: A FRα-targeting antibody–drug conjugate induces responses in patients with platinum-resistant tumors.
Approach: A phase I expansion cohort study evaluated IMGN853 in patients with FRα-positive platinum-resistant tumors.
Impact: Targeting FRα with IMGN853 may be safe and effective in patients with platinum-resistant ovarian cancer.
Most patients with epithelial ovarian cancer initially respond well to first-line platinum-based chemotherapy, but the majority of patients eventually relapse and new targeted therapies are needed. The folate receptor alpha (FRα) allows transport of folate into cells and is overexpressed in multiple epithelial tumors including ovarian cancer, suggesting its potential as a therapeutic target. FRα can be targeted by mirvetuximab soravtansine (IMGN853), an antibody–drug conjugate that targets FRα with a monoclonal antibody fused to a cytotoxic agent, which has exhibited antitumor activity in preclinical studies. To evaluate the safety and clinical activity of IMGN853, Moore and colleagues enrolled 46 patients with FRα-positive platinum-resistant tumors, 43 of whom had epithelial ovarian cancer, in a phase I expansion cohort study. IMGN853 was well tolerated and adverse events were generally mild, with serious treatment-related adverse events occurring in only 11 patients (22%). Confirmed objective responses were observed in 12 patients (26%), including 1 complete response and 11 partial responses. The median progression free survival was 4.8 months, and the median duration of response was 19.1 weeks. Patients who had received 3 or fewer prior lines of therapy responded better to IMGN853, achieving an objective response rate of 39%, a progression-free-survival of 6.7 months, and a median duration of response of 19.6 weeks. Taken together, the results of this phase I trial suggest that IMGN853 is safe and has clinical activity in patients with platinum-resistant ovarian cancer, and has similar efficacy to that observed with standard single-agent chemotherapy. Based on these findings, IMGN853 is being investigated further in a single-agent phase III trial in patients with platinum-resistant disease.
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