CheMo4METPANC: A phase 2 study with combination chemotherapy (gemcitabine and nab-paclitaxel), chemokine (C-X-C) Motif receptor 4 inhibitor (motixafortide), and immune checkpoint blockade (cemiplimab) in metastatic treatment-naïve pancreas adenocarcinoma.

• DOI: 10.1200/jco.2023.41.16_suppl.tps4200
• Publication Date: 2023-06-04T15:37:26Z
• Authors: Gulam Abbas Manji; Michael S. May; Ilenia Pellicciotta; Sarah Sta Ana; Naomi Sender; Samuel M Pan; Isabelle Ross; Jianhua Hu; Qian Shi; Alexander G Raufi
• Keywords: Immune checkpoint

TPS4200 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a uniformly fatal disease for which treatments result in limited benefit. Failure of immune checkpoint blockade attributed to multiple immunosuppressive pathways within the tumor microenvironment. The C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C ligand 12 (CXCL12) axis results exclusion anti-tumor cells. Preclinical studies demonstrated that simultaneous CXCR4 inhibition (CXCR4i) and anti-programmed cell death 1 (aPD1) resulted stabilization. We extended these findings by testing combinations CXCR4i, aPD1, gemcitabine KPC mouse model PDAC. Mice treated with gemcitabine, aPD1 (triple therapy) experienced survival benefit compared mice either alone, or CXCR4i/aPD1. Tumors from triple therapy increased apoptosis favorable microenvironment (TIME). Motixafortide pembrolizumab, fluorouracil, nanoliposomal irinotecan has shown encouraging second-line setting mPDAC confirmed ORR 13.2% progression free (PFS) 3.8 months (m). goal this first-in-man trial test preliminary safety efficacy (CXCR4i), Cemiplimab (aPD1), Gemcitabine, Nab-paclitaxel (MCGN) treatment naïve mPDAC. Methods: This an open label, multicenter, investigator-initiated simon-2-stage phase 2 clinical MCGN. study includes six-patient run-in cohort additional patients comprising pilot signal seeking (N=10). If ≥3 10 stage were experience partial response (PR) RECIST criteria 16 weeks, combination would be considered promising expansion 30 was planned. On 09/21/22, we amended forego planned open-label (N=30) transition directly randomized MCGN toGemcitabine (GN) alone (N=102), after completion study. primary endpoint PFS. 80% power detect improvement PFS 6 9.2 m (HR 0.65) one-sided alpha 0.20. One interim analysis futility when 50% events are observed. Secondary objectives include ORR, control rate, duration OS. Required (pilot portion) optional (randomized paired biopsies will undergo exploratory including interrogation TIME. started September 2020 enrolled as 02/2023. Clinical information: NCT04543071 .