Single-center phase 1-2 trial of neoadjuvant BMS-813160, nivolumab and chemotherapy for borderline resectable or locally advanced PDAC

Targeting tumor-associated macrophages through C-C chemokine receptor (CCR) type 2 in pancreatic ductal adenocarcinoma (PDAC) improves the efficacy of chemotherapy in preclinical models. A phase 1-2 trial at Washington University in St. Louis (MO) evaluated the neoadjuvant combination of gemcitabine and nab-paclitaxel (GnP) chemotherapy, the CCR2/5 inhibitor BMS-813160, and nivolumab for borderline resectable (BR) or locally advanced (LA) PDAC. Eight patients received GnP alone (control group) and 31 patients (29 response evaluable) received the combination. No grade 3 or 4 toxicities attributed to nivolumab or BMS-813160 were observed. After 4 neoadjuvant cycles, the ORR was 35.7% among BR-PDAC patients and 16.7% among LA-PDAC patients, compared with 0% among control patients. Among patients who completed study treatment, 78.8% of BR- and 16.7% of LA-patients underwent surgical resection. Median progression-free and overall survival were 14.6 and 20.4 months, respectively, among BR-PDAC patients and 14.7 and 17.0 months, respectively, among LA-PDAC patients. The authors conclude that the combination was well tolerated and warrants a larger phase 2 trial.