<p>Supplementary Table 1. Antibodies used in flow cytometry.</p>
ARTICLE ABSTRACT
Targeting tumor-associated macrophages through C–C chemokine receptor type 2 (CCR) in pancreatic ductal adenocarcinoma (PDAC) improves the efficacy of chemotherapy and restores T-cell immunity in preclinical models.
We conducted a phase I/II single-institution study (NCT03496662) combining chemotherapy gemcitabine and nab-paclitaxel (GnP), CCR2/5 inhibitor BMS-813160, and nivolumab for four 28-day cycles for patients with borderline resectable (BR) or locally advanced (LA) PDAC. The recommended phase II dose of BMS-813160 was established in the 3 + 3 design. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included resection rate, median progression-free survival, and median overall survival.
Eight patients were treated with GnP alone (control arm), and 32 patients (29 response evaluable) were treated at the recommended phase II dose. One instance each of grade 3 diarrhea and QTc prolongation occurred which were atrributed solely to BMS-813160. After four cycles of study treatment (N = 22), the ORR was 42% and 20% among patients with BR and LA PDAC, respectively, compared with 0% of control patients. A total of 83.3% of patients with BR and 20% of patients with LA PDAC who completed study treatment underwent surgical resection. For intent-to-treat analyses, patients with BR PDAC had a median progression-free survival and median overall survival of 11.9 and 18.2 months, respectively, whereas patients with LA PDAC had 14.7 and 17 months, respectively. Biomarker analyses showed decreased intratumoral monocytes and macrophages and enhanced T-cell proliferation and effector gene expression.
Neoadjuvant BMS-813160/nivolumab/GnP was well tolerated and seems to achieve comparable ORR and resectability with historical data; however, with prolonged PFS and OS in LA-PDAC patients, warranting a larger phase II study with a more efficacious CCR2-targeted therapeutic.
