Abstract A50: Phase Ib/II study of pembrolizumab plus chemotherapy: Initial results of metastatic cancer patients
Authors: Weiss Glen J. , Pierog Marci , Blaydorn Lisa , Sangal Ashish , Niu Jiaxin , Farley John H. , Khemka Vivek 
Published: May 2016

Abstract
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 naïve (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 (&gt;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.
Cohort detailsArm# of pts (cancer type)# DLTs (type)Current dose level (all arms: P 2 mg/kg on day 1 plus):Phase 2 dose open?BOR (duration in months) for evaluable pts17 (3 ER+ breast cancer [BC], 2 triple negative BC [TNBC], 1 small cell lung cancer [SCLC], 1 cervical cancer)1 (gr3 neutropenia)G 1000 mg/m2 on days 1 and 8Yes6 PD, 1 too early21 (EGFR/KRAS/ALK wildtype [WT] lung adenocarcinoma [NSCLC]NoneG 900 mg/m2 on days 1 and 8 + D 75 mg/m2 on day 8No1 too early3a (chemo naïve pts)2 (pancreatic adenocarcinoma [PDAC])NoneG 1000 mg/m2 + NP 125 mg/m2 on days 1 and 8No1 PR (8+), 1 too early3b (previously treated pts)3 PDAC2 (gr3 thrombocytopenia and gr3 fatigue and thrombocytopenia)G 800 mg/m2 + NP 100 mg/m2 on days 1 and 8No2 SD (5, 6), 1 too early48 (3 sarcoma, 2 ER+ BC, 1 ER/HER+ BC, 1 TNBC, 1 WT NSCLC)2 (gr3 hypoxia and gr3 neutropenia)G 800 mg/m2 + V 20 mg/m2 on days 1 and 8No2 SD (2+, 3), 3 PD, 2 too early59 (3 SCLC, 3 KRAS+ NSCLC, 2 EGFR+ NSCLC, 1 WT NSCLC)3 (gr3 fatigue, gr3 nausea and vomiting, gr3 rash and papilledema)I 250 mg/m2 on day 1No2 PR (7+, 7+), 1 SD (4+), 3 PD, 2 too early67 (3 sarcoma, 2 ovarian cancer, 1 endometrial cancer, 1 ER+ BC)NoneLD 30 mg/m2 on day 1No3 SD (3, 3+ 6+), 1 PD, 3 too early
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.