An open-label phase I dose-escalation study of the safety and pharmacokinetics of DMUC4064A in patients with platinum-resistant ovarian cancer

Objectives: MUC16 is overexpressed in the majority of human epithelial ovarian cancers (OC). DMUC4064A is a humanized anti-MUC16 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. This trial assessed the safety, tolerability, pharmacokinetics, and preliminary activity of DMUC4064A in patients with platinum-resistant OC. Methods: DMUC4064A was administered once every 3 weeks to patients in 1.0–5.6 mg/kg dose escalation cohorts, followed by cohort expansion at the recommended Phase II dose (RP2D). Results: Sixty-five patients were enrolled and received a median of 5 cycles (range 1–20) of DMUC4064A. The maximum tolerated dose was not reached; 5.2 mg/kg was the RP2D based on the overall tolerability profile. The most common adverse events were fatigue, nausea, abdominal pain, constipation, blurred vision, diarrhea, and anemia. Sixteen patients (25%) experienced related grade ≥ 3 toxicities. Twenty-six patients (40%) experienced ocular toxicities. The exposure of acMMAE was dose proportional, with a half-life of ~6 days. Sixteen patients (25%) experienced confirmed objective partial response (PR or CR) starting at ≥3.2 mg/kg dose levels, while 23 (35%) patients had best responses of PR or CR. Overall, the clinical benefit rate was 42% (27 patients with a best response [confirmed and unconfirmed] of CR, or PR or SD lasting ≥6 months). Among the 54 patients with high MUC16 immunohistochemistry scores, the clinical benefit rate was 46% (25 patients). Median progression-free survival was 3.9 months overall. Conclusions: In this Phase I study, DMUC4064A demonstrated a tolerable safety profile along with encouraging efficacy in the indication of platinum-resistant OC.