Phase I/Ii Trial Of Gemcitabine, Nab-Paclitaxel, And Pembrolizumab In Metastatic Pancreatic Adenocarcinoma

Background: Pembrolizumab (P) is a checkpoint inhibitor that blocks the interaction between programmed cell death protein 1 on T-cells and PD-L1 and PD-L2 on tumor cells. We conducted a single center phase Ib/II study of gemcitabine, nab-paclitaxel, and P (GNP) to evaluate the safety and efficacy in metastatic pancreatic adenocarcinoma (PDAC) (NCT02331251). Methods: PDAC patients (pts) with measurable disease, biopsy proven metastasis, adequate laboratory tests, and KPS ≥ 70% were eligible and received gemcitabine and nab-paclitaxel on days 1 and 8 and P 2 mg/kg on day 1 every 21 days until progression or toxicity. Safety monitoring, RECIST 1.1, and irRECIST assessments were conducted. Response imaging was performed prior to cycle 4, then every 3 months. Results: 17 pts with a median age of 56 were treated. 11 were women and all had a KPS of at least 80%. Any grade drug-related treatment adverse events (AEs) occurred in 100% of patients; the most common (u003e20% pts) were anemia, thrombocytopenia, hypoalbuminemia, ALT and ALK elevation, fatigue, rash, nausea, vomiting, diarrhea, fever, insomnia, and edema in limbs. Grade 3 events (u003e10% pts) were hyponatremia, thrombocytopenia, and neutropenia (2 case each, 11.8%). Dose-limiting toxicities occurred only in previously treated PDAC (grade 3 thrombocytopenia; grade 3 fatigue and thrombocytopenia) and the cohort was subsequently divided into chemo naive and previously treated pts. The recommended phase II dose (RP2D) for chemo naive PDAC was gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2. Of the 8 evaluable chemo naive PDAC, the disease control rate (partial response [PR] + stable disease[SD]) was 100%. There were 2 PR on treatment for ~11 and 15 months and there are 3 pts still too early to assess. The primary endpoint of u003e15% complete response was not met. The best response for previously treated pts was SD. For chemo naive and previously treated PDAC, the 6-month survival rate is 89% (with 3 pts still on study less than 3 months) and 40%, respectively. The median PFS and OS is 5 and 10.3 months and 2.1 and 4.1 months for chemo naive and previously treated pts, respectively. Conclusions: GNP can be safely given to chemo naive PDAC pts. Efficacy appears to be similar to slightly improved over previously reported results for standard weekly x 3 every 28 day gemcitabine and nab-paclitaxel dosing. Citation Format: Glen J. Weiss, Jordan Waypa, Jessica Coats, Lisa Blaydorn, Kayla McGahey, Ashish Sangal, Robert P. Whitehead, Vivek Khemka. Phase I/II trial of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT134. doi:10.1158/1538-7445.AM2017-CT134