Abstract 7141: Final analysis of the randomized Phase 2 cohort of CM24 with nivolumab and chemotherapy in pancreatic cancer &amp; potential serum biomarkers
Authors: Teresa Macarulla, Michael Cecchini, Rocio Garcia-Carbonero, Talia Golan, Ruth Perets, Erkut Borazanci, Manuel Pedegral, Mariano Ponz-Sarvisé, Mohammed Najeeb Al Hallak, Shubham Pant, Valentina Boni, Omar Saavedra, María José de Miguel-Luken, Alexis D Leal, Andrés J. Muñoz, Tamara Sauri-Nadal, Hava Ben David, Tomer Meirson, Micheal Schickler, Hadas Reuveni
Journal: Cancer Research (2025)

Abstract Background: CM24 (mAb) blocks CEACAM1 interactions between cancer cells, immune cells and neutrophil extracellular traps (NET), involved in tumor immune evasion, metastasis and cancer-associated thrombosis, affecting patient (pts) survival. We present the final data for the randomized Phase 2 study (NCT04731467) and significant efficacy in a biomarker-enriched subgroup. Methods: Advanced/metastatic PDAC pts (n=31) progressing after first line treatment, were randomized to receive CM24 (20mg/kg q2wk), nivolumab (240mg/kg q2wk) and chemotherapy (liposomal irinotecan/5FU/LV) (EXP) vs chemotherapy only (CON; q2wk). Pre-dose serum samples (n=30) were collected. Serum CEACAM1 and myeloperoxidase (MPO; a NET marker) levels were evaluated by ELISA. Biomarkers were analyzed post-hoc and HRs for various thresholds were correlated with survival outcomes to select the greatest range providing a statistical benefit. The selected ranges exclude pts with extremely low or high levels of CEACAM1 and NETs. Results: Final analysis of EXP vs CON shows OS 7.9m vs 5.6m (Δ=2.3m) HR 0.81 (P 0.575, CI 0.38-1.71), PFS 3.9m vs 2.0m (Δ=1.9m) HR 0.75 (P 0.46, CI 0.35-1.61), ORR 25% vs 6.7%, DCR 62.5% vs 46.7%. Most frequent Grade ≥3 adverse events were diarrhea; 4 vs 1 pts, fatigue; 2 vs 0 pts and neutropenia; 2 vs 0 pts. Subgroup analysis of pts with serum CEACAM1 level of 6K-15K pg/mL (n=11/30) demonstrates statistically significant benefits in terms of OS: HR 0.21 (P 0.04, CI 0.04-1.06), ΔOS=5.1m, PFS: HR&amp;lt;0.1 (P 0.003, CI 0-inf), ΔPFS=2.9m, and ORR 50% vs 0%. Statistically significant results were also seen for 80% of the pts (24/30) with serum CEACAM1 (5-16K pg/mL) or serum NET marker MPO (200-600 ng/mL) demonstrating OS HR 0.39 (P 0.039, CI 0.16-0.98) and PFS HR 0.28 (P 0.006, CI 0.11-0.73). Conclusions: Final data show that adding CM24 and nivolumab to chemotherapy improved all efficacy parameters and had a manageable safety profile. Subgroup analyses demonstrate statistically significant reduction in the risk of OS and PFS, and suggest serum CEACAM1 &amp; NET marker as predictive biomarkers for CM24-based therapy, corresponding with CM24 mechanism of action Citation Format: Teresa Macarulla, Michael Cecchini, Rocio Garcia-Carbonero, Talia Golan, Ruth Perets, Erkut Borazanci, Manuel Pedegral, Mariano Ponz-Sarvisé, Mohammed Najeeb Al Hallak, Shubham Pant, Valentina Boni, Omar Saavedra, María José de Miguel-Luken, Alexis D Leal, Andrés J. Muñoz, Tamara Sauri-Nadal, Hava Ben David, Tomer Meirson, Micheal Schickler, Hadas Reuveni. Final analysis of the randomized Phase 2 cohort of CM24 with nivolumab and chemotherapy in pancreatic cancer &amp; potential serum biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7141.