Introduction: A selective anti-PD-1 antibody, nivolumab (N), blocks the interaction between programmed death-1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumor cells. We report safety and clinical activity of N combined with capecitabine and irinotecan (CAPIRI) in patients with previously treated metastatic colorectal cancer (CRC) and pancreatic ductal adenocarcinoma cancer (PDAC) (NCT02423954).
Methods: Patients (pts) were treated with N 3 mg/kg on day 1 and day 15 every 28 day cycle along with CAPIRI until disease progression or toxicity. Eligibility included ≥1 measurable tumor lesion, Karnofsky Performance Status (KPS) of ≥70%, and adequate organ function. Tumors were assessed every 3 cycles using RECIST 1.1 and immune-related response criteria and best overall response (BOR) was evaluated.
Results: 12 patients were consented and 9 pts (8 CRC and 1 PDAC) have been enrolled at the time of submission. Median age was 52 (range 41-72) and median KPS was 90%. Any grade drug-related treatment adverse events (AEs) occurred in 100% of patients; the most common (>50% pts) were fatigue (grade 1), nausea (grade 1), diarrhea (grade 1). No infusion-related reactions were observed. Six patients are currently evaluable for BOR, with one partial response for 8 months as the BOR so far. One patient had stable disease (SD) for six months, one patient has ongoing SD for over 3 months, and three patients had disease progression. Three are still too early to evaluate. There were no dose limiting toxicities or study-related serious adverse events (SAEs). The recommended phase 2 dose is N 3 mg/kg on day 1 and day 15 every 28 day cycle along with CAPIRI (consisting of irinotecan 175 mg/m2 on day 1 every 14 days and capecitabine 1000 mg PO BID days 1-5 on, days 6-7 off, each 7 day period).
Conclusion: In pts with previously treated metastatic CRC or PDAC, N plus CAPIRI appears to be safe and the phase II portion has begun. Updated results will be presented at the conference.