Mirvetuximab soravtansine (Ms) is an antibody-drug conjugate (ADC) comprised of a folate receptor α (FRα)-targeting antibody linked to the maytansinoid DM4, which is a potent tubulin-disrupting agent.1 Previous studies have shown that Ms activates monocytes and upregulates immunogenic cell death markers on ovarian tumor cells, providing a rationale for combining this novel ADC with immune checkpoint inhibitors.2

Previously reported results from the phase 1b FORWARD II study, which evaluated Ms in combination with pembrolizumab in 14 patients with platinum-resistant ovarian cancer (PROC), demonstrated that this combination has favorable tolerability, with primarily low-grade (≤grade 2) adverse events observed.2 The overall safety profile of the combination was manageable and consistent with the known profiles of each agent. In addition, promising evidence of durable antitumor activity was observed, including a confirmed objective response rate of 43%, median duration of response of 6.9 months, and median progression-free survival of 5.2 months.2

Here, Matulonis and colleagues report initial results of an expansion cohort from the FORWARD II study, in which an additional 23 patients with PROC have been recruited to receive the Ms/pembrolizumab combination.3 Patients had PROC, defined as progression within 6 months of completion of platinum-containing therapy, had at least 1 lesion that meets the definition of measurable disease by RECIST 1.1 criteria, and were FRα-positive by immunohistochemistry. The primary objective was to evaluate the safety and tolerability of the combination of Ms + pembrolizumab in patients with PROC. Patients received pembrolizumab 200 mg + Ms 6 mg/kg on day 1 of a 3-week cycle. At a median follow-up of 8.3 months, the overall response rate was 30% in the total patient population and 31% in those within these 2 groups, respectively. The majority of adverse events were grade 1 or 2 and manageable. Grade 3 and 4 adverse events were seen in 38% and 7%, respectively. Pneumonitis, considered an adverse event of special interest, was observed in 10 patients, 8 of which were grade 1 or 2.

Preliminary data from FORWARD II have demonstrated a manageable safety profile and encouraging signals of clinical activity for the Ms/pembrolizumab combination in recurrent PROC. The results of this expansion cohort will guide further development of this novel combination.

References

  1. Moore KN, et al. Future Oncol. 2018;14:1669-1678.
  2. Matulonis UA, et al. Society of Gynecologic Oncology 2018. Abstract 74.
  3. Matulonis UA, et al. ESMO 2018. Abstract 949P.  
Last modified: October 22, 2018