A phase I/II study of chemo-immunotherapy with durvalumab (durva) and pegylated liposomal doxorubicin (PLD) in platinum-resistant recurrent ovarian cancer (PROC)

Abstract

Background: Programmed cell death ligand 1 (PD-L1) expression and preliminary evidence of antitumor activity with anti-PD-1 therapy have been reported in ovarian cancer. PLD, a pegylated, liposomal form of doxorubicin, is a standard option for this population; durva is an anti-PD-L1 antibody. The primary objectives of this study are to determine the safety of the combination and to evaluate clinical efficacy by progression- free survival rate at 6months (PFS6) using RECIST 1.1. Methods: This is a phase 1/2, multicenter, open-label study (NCT02431559) of durva in patients (pts) with PROC, scheduled to receive PLD. The study includes a dose escalation (phase 1: 3 +3 design; DLT evaluation over one 28-day cycle; n=6-18) and a dose expansion (phase 2: n=41). PLD has been reported to have a 25% PFS6. A sample size of 41 evaluable pts yields 80% power to test the null hypothesis of a PFS6 rate of≤25% against the alternative hypothesis of a PFS rate of≥45% at an alpha level of 0.05 (one-sided). Blood and tumor samples were also collected for assessment of correlative immunologic responses. Results: First pt dosed: 09Aug2016. As of 05Mar2018, 40 female pts (median age: 65 [32-83] years) were enrolled in phase 2 of the study; each received at least 1 dose of study therapy (PLD 40 mg/m2+durva 1500 mg Q4W) and are included in the safety analyses. Most frequent (in≥25% pts) treatment-emergent adverse events (AEs, all causality) were palmar-plantar erythrodysesthesia syndrome (PPES)/rash, stomatitis, fatigue, abdominal pain, nausea, pyrexia, and vomiting. Grade 3 treatment-related AEs in≥2 pts included PPES/rash, stomatitis, lymphocyte count decreased, lipase increased, and anemia. As of the cutoff date, 33 pts reached the timepoint for PFS6 assessment. Twelve pts were progression-free at 6 months; PFS6= 30% (12/40 pts). The remaining data will mature by July 2018, and further improvement in PFS6 may occur. Updated PFS6 and preliminary correlative results will be presented at the meeting. Conclusions: The combination of durva and PLD in women with PROC appears to have a tolerable safety profile and promising efficacy. PFS6 and translational endpoints are pending additional data.