Dr Cecchini on the Initial Efficacy of CM24 Plus Nivolumab and NALIRIFOX in Advanced PDAC

Michael Cecchini, MD, assistant professor, medicine, Medical Oncology, co-director, Colorectal Program, the Center for Gastrointestinal (GI) Cancers, Yale School of Medicine, medical oncologist, Yale Medicine, discusses interim efficacy and safety data from the phase 2 FW-2020-01 study (NCT04731467) in advanced/metastatic pancreatic ductal adenocarcinoma (PDAC).

The global multicenter, open-label, randomized study evaluated the novel CEACAM1-targeted monoclonal antibody CM24 with nivolumab (Opdivo) and liposomal irinotecan, 5-fluorouracil, and leucovorin (NALIRIFOX) vs NALIRIFOX alone in patients with advanced/metastatic PDAC following progression on or during first-line therapy, Cecchini begins.

At the 2024 ASCO Annual Meeting, results from the trial demonstrated significant improvements in progression-free survival (PFS), overall survival (OS), and response rates with the addition of CM24 and nivolumab to the NALIRIFOX regimen in the second-line treatment setting, he reports. The median OS was 7.72 months (95% CI, 4.00-8.11) with the experimental regimen compared with 5.62 months (95% CI, 3.22-7.89) in the control arm, Cecchini details. This resulted in a hazard ratio of 0.74 (95% CI, 0.31-1.77), translating to a 26% reduction in the risk of death or disease progression.

Furthermore, the median PFS was doubled from 1.9 months (95% CI, 1.8-5.0) in the control arm to 3.8 months (95% CI, 0.9-3.6) in the investigational arm, with a hazard ratio of 0.72 (95% CI, 0.33-1.60), corresponding to a 28% reduction in the risk of death or progression, Cecchini adds. Response rates were significantly higher in the investigational arm at 25% vs 6.7% in the control arm, and the disease control rate was 62.5% vs 40.0% with the experimental vs control regimens, respectively. This showed that all efficacy measures favored the investigational regimen, Cecchini explains.

The addition of CM24 to nivolumab and NALIRIFOX was also well tolerated. The interim analysis suggests that the combination of CM24, nivolumab, and NALIRIFOX has a manageable safety profile and offers longer PFS, supported by higher objective response rates (ORR) and disease control rates (DCR). OS data continue to mature with further analyses.

The combination therapy could represent a promising second-line treatment option for patients with advanced/metastatic PDAC.