A Phase 1 clinical trial and single-cell correlates of motixafortide, cemiplimab, gemcitabine and nab-paclitaxel for metastatic treatment-naïve metastatic pancreatic ductal adenocarcinoma.

Building on pre-clinical data demonstrating a survival benefit with the addition of gemcitabine to CXCR4 and PD1 inhibition in the KPC mouse model, we conducted an open-label, single-arm phase 1 clinical trial combining CXCR4 inhibition (motixafortide), PD-1 blockade (cemiplimab), and chemotherapy (gemcitabine/nab-paclitaxel; MCGN) in treatment-naïve patients with metastatic PDA (n=11).

MCGN was safe and tolerable, achieving a 64% partial response (PR) by iRECIST, a 55% confirmed partial response (cPR), and a 91% disease control rate (DCR). The median PFS and OS were 9.7 months (95% confidence interval [CI]: 5.9-not reached [NR]) and 10.1 months (95% CI: 9.3-NR), respectively. One patient achieved a pathological complete response within the primary tumor and the hepatic metastasis after undergoing a pancreatoduodenectomy and hepatectomy and has remained free of disease for 18 months, suggesting that durable responses are possible with MCGN treatment.