Abstract 47P
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 (D=2.3m) HR 0.81 (P 0.575, CI 0.38-1.71), PFS 3.9m vs 2.0m (D=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), DOS=5.1m, PFS: HR<0.1 (P 0.003, CI 0-inf), DPFS=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 & NET marker as predictive biomarkers for CM24-based therapy, corresponding with CM24 mechanism of action.
Clinical trial identification
NCT04731467.
Editorial acknowledgement
Legal entity responsible for the study
Purple Biotech Ltd.
Funding
Purple Biotech Ltd.
Disclosure
T. Macarulla Mercade: Financial Interests, Personal, Advisory Board: Ability Pharmaceutical, SL, AstraZeneca, Basilea Pharma, Batxer, BioLineRX Ltd., Celgene SLU, Eisai, IPSEN Pharma, Incyte; Financial Interests, Personal, Other, Direct research fund: Servier, Merck, Sharp and Dhome, Novocure, QED Therapeutics Inc, Roche, Sanofi-Aventis, Zymeworks; Financial Interests, Personal, Invited Speaker: Lilly, Janssen; Financial Interests, Institutional, Research Grant: Amc Medical Research, Armo Biosciences, Basilea, Biokeralty Research Institute, Merck Sharp & Dohme, Oncomed Pharmaceuticals, QED Therapeutics, VCN Biosciences, AbbVie Farmaceútica, Ability Pharmaceuticals, Agios, Amgen, Aslan, AstraZecena, Bayer, Beigene, Biolinerx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb (BMS), Cantargia, Celgene, Eisai, Erytech Pharma, F. Hoffmann-la Roche, Fibrogen, Genentech, Hallozyme, Immunomedics, Incyte, Ipsen, Lab. Menarini, Lilly, Loxo Oncology, MedImmune, Merimarck, Millenim, Nelum, Novartis, Novocure, Pfizer, Pharmacyclics, Roche, Zymeworks; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology - ASCO, “Sociedad Española de Oncología Médica” – SEOM, Sociedad Europea de Oncología Médica - ESMO; Other, Personal, Other, Editorial Board: GI Annals og¡f Oncology. M. Cecchini: Financial Interests, Personal, Advisory Board, Honoraria for advisory board: Eisai Co, Agios Pharmaceuticals, DAVA Oncology, Bayer Pharmaceuticals, Seattle Genetics, Macrogenics, Taiho, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Advisory Board: Agenus, Elevate Oncology, Regeneron, Loxo@Lily, Incendia Therapeutics. R. Garcia-Carbonero: Financial Interests, Personal, Advisory Board: AAA, Advanz Pharma, Amgen, Astellas, Bayer, BMS, Boerhringer, Esteve, Hutchmed, Ipsen, Midatech Pharma, MSD, Novartis, PharmaMar, Pierre Fabre, Servier, Takeda; Financial Interests, Institutional, Research Grant: BMS, MSD, Pfizer; Non-Financial Interests, Personal, Leadership Role, Global PI of investigator-initiated clinical trials (AXINET, NICENEC, PEMBROLA): BMS, MSD, Pfizer; Non-Financial Interests, Personal, Leadership Role, Chair: European Neuroendocrine Tumor Society (ENETS); Non-Financial Interests, Personal, Leadership Role, Past president, Member of the Executive Committee: Grupo Español de Tumores Neuroendocrinos (GETNE); Other, Personal, Other, Honoraria received by spouse for advisory board or invited speaker roles: ABBIE, AstraZeneca, Bayer, Boehringer, BMS, Genomica, Lilly, MSD, Merck, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, Takeda. T. Golan: Financial Interests, Personal, Advisory Board: AstraZeneca, AbbVie, Merck MSD; Financial Interests, Institutional, Other, Grant: AstraZeneca; Financial Interests, Institutional, Other, grant: AbbVie; Financial Interests, Personal, Invited Speaker: ClearNote; Financial Interests, Personal, Stocks/Shares: Curesponse. M.S. Ponz: Financial Interests, Personal, Advisory Board: Taiho, AstraZeneca; Financial Interests, Institutional, Funding: Roche, Novocure; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Other, imFLAME Committee member: Roche. M.N. Al-Hallak: Financial Interests, Personal, Invited Speaker: Ipsen, AstraZeneca, Guardant Health, Takeda, Seagen, Purple Biotech, Amgen, Incyte Corporation, Merus, Mirror Biologics, Tvardi, Astellas, Roche, 23andMe, Inc, NuCana, Refmal; Financial Interests, Personal, Research Grant: Purple Biotech, U CAN-CER VIVE Foundation; Financial Interests, Personal, Invited Speaker, Invited Speaker: AstraZeneca. M. De Miguel: Financial Interests, Institutional, Invited Speaker: Janssen, MSD; Non-Financial Interests, Personal, Principal Investigator: Janssen, MSD, Roche, PharmaMar, Replimune, Novartis, Abbvie, Achilles, Amunix, Arcus, Furmo, Biontech, Catalym, Dizal, Genentech, Loxo, Numab, Seagen. A.J. Munoz Martin: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, Sanofi, Celgene, Servier, MSD, Pfizer, Leo Pharma, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Rovi, STADA, Menarini, BMS; Financial Interests, Institutional, Invited Speaker, VTE risk assessment model: Genincode; Financial Interests, Institutional, Invited Speaker: Celgene. T. Sauri Nadal: Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Personal, Advisory Board: Amgem. H. Ben David, M. Schickler, H. Reuveni: Financial Interests, Institutional, Full or part-time Employment, employee: Purple Biotech Ltd. T. Meirson: Financial Interests, Personal, Full or part-time Employment, Personal fees: Purple Biotech. All other authors have declared no conflicts of interest.