Background: Cytotoxic chemotherapy activates the immune system through multiple mechanisms, including stress signaling, antigen release by dying tumor cells, and modulation of immune cell populations. Nivo, an anti–PD-1 antibody, has demonstrated activity in other solid tumors but has not yet demonstrated activity in PC. The combination of nab-P + G is approved by the US Food and Drug Administration as first-line therapy for metastatic PC (MPC). nab-P does not require corticosteroid pretreatment, which makes it a suitable combination partner with nivo to test for safety and efficacy in PC. Here we report interim results from the first of 2 PC cohorts of a Phase 1 study of nivo + the standard dose and schedule of nab-P.

Methods: The 2 PC cohorts (arms A and B) were to be initiated sequentially. In arm A, patients with locally advanced PC (LAPC) or MPC who had received 1 prior chemotherapy regimen received nab-P 125 mg/m2 on days 1, 8, and 15 of a 28-day cycle (qw 3/4) in combination with nivo 3 mg/kg on days 1 and 15 of the 28-day cycle starting with cycle 1. The primary objective of part 1 was to identify dose-limiting toxicities (DLTs). Patients treated with ≥ 2 cycles of nivo + nab-P or who discontinued due to a DLT prior to completing 2 cycles of nivo + nab-P were considered DLT evaluable. If arm A is deemed safe per DLT evaluation, arm B will enroll chemotherapy-naive patients, who will receive G 1000 mg/m2 qw 3/4 in addition to nivo + nab-P.

Results: Between February 24 and December 3, 2015, 11 patients were enrolled in arm A. Most patients were < 75 years of age (82%) and male (55%). No DLTs were observed, and no grade 3/4 AEs occurred in > 1 patient. Among 8 response-evaluable patients, 1 had a partial response and 4 achieved stable disease. Eight patients discontinued treatment due to disease progression.

Conclusions: In arm A of the PC cohort, the addition of nivo to nab-P did not appear to increase safety/tolerability concerns. Based on safety observed in arm A, arm B will enroll patients with MPC for first-line treatment with nivo + nab-P + G. ClinicalTrials.gov: NCT02309177.

Citation Format: Howard S. Hochster, Zev A. Wainberg, Martin Gutierrez, David Waterhouse, E Gabriela Chiorean, Ben George, Amy Ko, Victoria Manax, Sotirios Stergiopoulos, Peter O’Dwyer.{Authors}. Phase 1 study of nivolumab (nivo) + nab-paclitaxel (nab-P) ± gemcitabine (G) in pancreatic cancer (PC): safety evaluation of patients treated with nivo + nab-P in arm A. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A72.