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 6 months (PFS6) using RECIST 1.1.
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.
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.
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.
Clinical trial identification
NCT02431559. May 1st 2015.
Legal entity responsible for the study
Ludwig Institute for Cancer Research.
Ludwig Institute for Cancer Research, Cancer Research Institute with funding also from VentiRx, and Medimmune. This study was funded in part through the NIH/NCI Support Grant P30 CA008748.
A. Wolfer: Advisory board: AstraZeneca. J.K. Bryan: CMO Novella Clinical, a contract research organization (January 2017-present); Previously CMO VentiRx Pharmaceuticals (2013-2016), with neither equity nor patent ownership on the technology at VentiRx. B.J. Monk: Consultant and speaker: AstraZeneca; Received honoraria for services. All other authors have declared no conflicts of interest.