A phase 2 trial of the human PD-1 receptor monoclonal antibody nivolumab has demonstrated efficacy for the treatment of platinum-resistant ovarian cancer. NINJA is a phase 3 trial conducted in Japan that aims to confirm efficacy and assess safety of nivolumab in this patient population.
The NINJA trial is a multicenter, open-label, randomized phase 3 study comparing nivolumab versus gemcitabine (GEM) or pegylated liposomal doxorubicin (PLD) for patients aged ≥20 years with advanced or recurrent platinum-resistant ovarian cancer who have not been previously treated with GEM/PLD. Patients were randomized (1:1) to receive nivolumab 240 mg intravenously every 2 weeks or to receive either GEM 1000 mg/m2 intravenously for 30 minutes on days 1, 8, and 15, then every 4 weeks or PLD 50 mg/m2 intravenously every 4 weeks. Randomization occurred after patients were stratified for histologic type (clear-cell carcinoma vs others) and number of prior chemotherapy regimens after diagnosis of resistance (0 or 1) to ensure equal distribution in treatment arms. Treatment was continued until disease progression or toxicity leading to discontinuation. Tumor burden was assessed every 8 weeks through 48 weeks, and every 12 weeks thereafter. The primary end point of NINJA was overall survival, and key secondary end points were progression-free survival and safety.
In total, 316 patients were randomized, 157 to the nivolumab arm and 159 to the GEM/PLD arm. For the patient population, 77.8% had ≥2 chemotherapies prior to study initiation and 14.2% had an Eastern Cooperative Oncology Group performance score of 1. The primary tumor site was the ovary (approximately 80% of patients), while approximately 20% of patients had clear-cell carcinoma. The median overall survival for the nivolumab arm was 10.12 months (95% confidence interval [CI], 8.34-14.09) versus 12.09 months (95% CI, 9.26-15.34) for the GEM/PLD arm. There was no statistically significant difference between the groups (hazard ratio [HR], 1.03; 95% CI, 0.80-1.32; P = .808). Median progression-free survival was 2.04 months (95% CI, 1.91-2.20) versus 3.84 months (95% CI, 3.58-4.17) for nivolumab and GEM/PLD, respectively (HR, 1.46; 95% CI, 1.15-1.85; P = .002). There was no statistically significant difference in response rate between the treatment groups; 8% in the nivolumab group versus 13% for the GEM/PLD group (odds ratio, 0.6; 95% CI, 1.02-1.3; P = .191). For patients who responded, the median duration of overall response was longer for the nivolumab group (n = 9) compared with the GEM/PLD group (n = 15), with durations of 18.7 months versus 7.4 months, respectively.
The rate of treatment-emergent grade 3/4 adverse events (AEs) was lower in the nivolumab arm (22.4%) versus the GEM/PLD arm (68.4%), as was the rate of all-grade AEs, 62% versus 98% for the nivolumab group versus the GEM/PLD group, respectively. In the nivolumab arm (n = 156), the most common major AEs (all grades) were rash (10%), fatigue (9%), nausea (6%), diarrhea (6%), and pruritus (6%).
Whereas nivolumab did not improve overall survival compared with GEM/PLD in this patient population, this study did suggest that it may show a prolonged response compared with GEM/PLD. Authors of the study are completing additional analyses to better understand the prolonged treatment response data. No new safety signals for nivolumab were observed in this trial, and nivolumab was well-tolerated compared with GEM/PLD, with decreased incidence and severity of AEs.
Abstract and Proffered Paper Presentation 807O. ESMO 2020. September 19-21, 2020. Nivolumab versus gemcitabine or pegylated liposomal doxorubicin for patients with platinum-resistant (advanced or recurrent) ovarian cancer: open-label, randomized trial in Japan (NINJA trial).