Abstract A50: Phase Ib/II study of pembrolizumab plus chemotherapy: Initial results of metastatic cancer patients

Background: A selective anti-PD-1 antibody, pembrolizumab (P), 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 P combined with chemotherapy in patients with metastatic cancer (NCT02331251). Methods: Patients (pts) with confirmed metastatic solid tumors were treated with P 2 mg/kg on day 1 every 21 day cycle on 1 of 6 different arms: gemcitabine (G) on days 1 and 8, G on days 1 and 8 + docetaxel (D) on day 8, G + nab-paclitaxel (NP) on days 1 and 8, G + vinorelbine (V) on days 1 and 8, irinotecan (I) on day 1, or liposomal doxorubicin (LD) on day 1 until 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: 37 pts have been enrolled at the time of submission (Table I). Median age was 55 (range 33-74) and median KPS was 80%. 3 patients (2 sarcoma, 1 ER+ breast cancer) had history of gemcitabine exposure before dosing on the G+V arm, and 2 patients with NSCLC had prior exposure to nivolumab for ≥ 2 months. The maximum tolerated dose (MTD) was exceeded for arms 3, 4, and 5 (Table I), and arm 3 dosing was subsequently divided into chemo naive (arm 3a) and previously treated (arm 3b) PDAC pts. Any grade drug-related treatment adverse events (AEs) occurred in 95% of patients; the most common (>10% pts) were skin rash, fatigue, diarrhea, anorexia, neutropenia, anemia, thrombocytopenia, and extremity edema. 1 infusion-related reaction was observed, related to LD. 24 patients are currently evaluable for BOR, 10 are still too early to evaluate. One PDAC pt is on G+NP for 8+ months with PR. Two SCLC pts continue on I for 7+ months with PR. 1 sarcoma pts continue on LD for 3+ and 6+ months with SD. Conclusions: In pts with metastatic cancer, P plus chemotherapy appears to be safe. P plus G phase 2 has begun enrolling TNBC pts. We anticipate confirmation of the recommended phase 2 dose for ∼3 of the 6 arms by the time of the conference. Citation Format: Glen J. Weiss, Marci Pierog, Lisa Blaydorn, Ashish Sangal, Jiaxin Niu, John H. Farley, Vivek Khemka. Phase Ib/II study of pembrolizumab plus chemotherapy: Initial results of metastatic cancer patients. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A50.