Motixafortide (CXCR4 inhibitor) + cemiplimab (PD-1) + gem/nab-paclitaxel posts 55% confirmed ORR in 1L metastatic PDAC

Motixafortide is a CXCR4 antagonist intended to disrupt the CXCR4/CXCL12-driven immune-excluded PDAC microenvironment, paired here with the PD-1 antibody cemiplimab plus gemcitabine/nab-paclitaxel (MCGN). In an open-label, single-arm Phase 2 first-stage cohort of treatment-naïve metastatic pancreatic ductal adenocarcinoma (n=11; NCT04543071), confirmed RECIST ORR was 55%; the partial-response rate including unconfirmed responses was 64%, with median PFS 9.7 months (95% CI 5.9–NR), median OS 10.1 months (95% CI 9.3–NR), DCR 91%, and DoR 8.2 months; one patient had a pathological CR after pancreatoduodenectomy/hepatectomy and remained disease-free for 18 months without adjuvant therapy. Versus the gemcitabine/nab-paclitaxel SOC benchmarks from MPACT (ORR ~23%, median PFS 5.5 mo, median OS 8.5 mo), the response rate and PFS look higher in this small cohort, while OS appears in the usual frontline range; detailed Grade ≥3 toxicity/discontinuation rates were not provided in the abstract, limiting risk/benefit comparison to SOC.