Epithelial ovarian cancer (EOC; including epithelial ovarian, fallopian tube, and primary peritoneal cancer) continues to have the highest mortality rate of all gynecologic malignancies [1], and recurrent disease remains a significant clinical challenge. Patients who relapse 6 months or more after front-line, platinum-based chemotherapy often remain chemosensitive and have a high likelihood of responding to additional platinum-based therapy [2]. In this setting, platinum-based chemotherapy is typically administered in combination with pegylated liposomal doxorubicin (PLD), gemcitabine, or a taxane [[3], [4], [5], [6]]. Bevacizumab is also indicated for use in patients with platinum-sensitive recurrences, in combination with platinum-based chemotherapy, followed by single-agent bevacizumab as maintenance therapy [7]. Approval of this antiangiogenic agent was based on findings from the OCEANS and GOG-0213 trials, which showed that addition of bevacizumab to chemotherapy with bevacizumab continuation significantly improved progression-free survival (PFS)—and slightly improved overall survival (OS) in the case of GOG-0213—over chemotherapy alone [[7], [8], [9]].

In the search for novel therapeutic options for patients with recurrent EOC, folate receptor alpha (FRα) has been shown to be an effective target [10]. This receptor is commonly overexpressed in epithelial tumors, particularly in high-grade serous ovarian and serous endometrial cancers, in contrast to healthy adult tissues that generally exhibit more restricted FRα expression [11,12]. Thus, FRα is an attractive candidate for antibody-drug conjugate (ADC)-based therapeutic approaches.

Mirvetuximab soravtansine is an ADC comprising an FRα-binding antibody, cleavable linker, and the maytansinoid DM4 payload, a potent tubulin-targeting agent [13], that received accelerated approval from the US Food and Drug Administration (FDA) in November 2022 for FRα-positive platinum-resistant EOC [14,15]. Importantly, mirvetuximab soravtansine exhibits a differentiated and manageable safety profile compared with standard-of-care chemotherapy in patients with advanced EOC that consists primarily of low-grade gastrointestinal, neurosensory, and resolvable ocular events that can be mitigated by appropriate supportive care and dose modifications [[16], [17], [18], [19], [20]]. Moreover, mirvetuximab soravtansine monotherapy elicits a low incidence of myelosuppression, which underscores the suitability of this agent for use in combination-based therapeutic approaches [16,17,19].

The feasibility of combining mirvetuximab soravtansine with carboplatin as a novel doublet approach for optimizing response to platinum therapy in patients with FRα-positive platinum-sensitive disease was previously shown [21]. Separately, the mirvetuximab soravtansine plus bevacizumab combination was found to be a well-tolerated and highly active regimen in patients with EOC, irrespective of platinum status [[22], [23], [24]]. Here, we report the results of an expansion cohort of the phase 1b FORWARD II trial (NCT02606305) evaluating the clinical activity, safety, and tolerability of mirvetuximab soravtansine in combination with both carboplatin and bevacizumab in patients with recurrent, platinum-sensitive EOC.