On April 30, 2025 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance, reported that a poster presentation titled "Final analysis of the randomized Phase 2 cohort of CM24 with nivolumab and chemotherapy in pancreatic cancer & potential serum biomarkers" is being presented during the session "Liquid Biopsy: Circulating Nucleic Acids 4 / Predictive Biomarkers 1" at the Annual Meeting of the American Association of Cancer Research (AACR 2025) on Wednesday, April 30, 2025 (Press release, Purple Biotech, APR 30, 2025, View Source;id=347386&p=2372871&I=1206939-c7Z3G6f3m8 [SID1234652394]).
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"These statistically significant biomarker results, with up to a 90% reduction in risk of death over the control group, are highly encouraging and we believe warrant a biomarker-driven Phase 2b study," stated Purple Biotech CEO Gil Efron. "The new, previously unpublished data presented at AACR (Free AACR Whitepaper) demonstrate significant overall survival (OS) and progression-free survival (PFS) benefit for patients meeting the criteria of either serum CEACAM1 or tumor CEACAM1 biomarkers. With these final data reported, we believe CM24 could potentially be positioned as a therapy targeting CEACAM1 in cancers with large unmet needs."
At AACR (Free AACR Whitepaper) 2025, Purple Biotech presented final data from its randomized, controlled, open-label, multicenter Phase 2 study (NCT04731467), which established proof of concept in a biomarker-enriched subgroup of 31 patients with advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) who were post-first line therapy, and compared treatment with CM24 + nivolumab + Nal-IRI/5FU/LV against treatment with Nal-IRI/5FU/LV alone.
The following is a summary of the findings.
The combination of CM24, nivolumab and Nal-IRI/5FU/LV chemotherapy was well tolerated and demonstrated quantitative improvement in all efficacy parameters, including OS, PFS, objective response rate (ORR), disease control rate (DCR) and CA19-9, in previously treated PDAC patients.
Without consideration of biomarkers, a consistent improvement in the treatment arm compared to the control arm was observed, as follows:
Prolongation of 2.4 months in OS HR=0.81 (p-0.575) and prolongation of 1.9 months in PFS HR=0.75 (p=0.463) vs. control arm
Higher ORR in experimental arm vs control arm (25% vs 6.7%)
Higher DCR in experimental arm vs control arm (62.5% vs 46.7%)
Consistent and continuous decrease in CA19-9 was observed in experimental arm vs control arm increase
Biomarker results included the following:
A statistically significant benefit to patients with defined pre-treatment ranges of serum CEACAM1 or tumor CEACAM1 expression (H score) compared to the control arm (representing a subgroup of 52% of patients):
Subgroup analyses of 16/31 patients meeting the criteria of CEACAM1+Tumor cell H score 115-275 or serum CEACAM1 levels 6K-15K pg/mL
78% reduction in risk of death (HR 0.22, 95% CI 0.07-0.7, p=0.006) and 95% reduction in the risk of progression or death (HR 0.05, 95% CI 0.01-0.44, p=0.0003)
Prolongation of 3.7 months in OS and 2.9 months in PFS
Statistically significant results in patients with defined pre-treatment serum CEACAM1 or myeloperoxidase (MPO) levels (representing a subgroup of 80% of patients):
Subgroup analyses for 24/30 patients meeting the criteria of MPO levels 200-600 ng/mL or serum CEACAM1 levels 6K-15K pg/mL
61% reduction in risk of death (HR = 0.39, 95% CI 0.16-0.98, p=0.039) and 72% reduction in the risk of progression or death (HR=0.28, 95% CI 0.11-0.73, p=0.006)
Prolongation of 2.4 months in OS and 2.2 months in median PFS
A statistically significant benefit for CM24-nivolumab treatment in patients with high CEACAM1+Tumor cell H score and low PD-L1 CPS (representing a subgroup of 38% of patients):
Subgroup analyses of 10/26 patients meeting the criteria of high CEACAM1+Tumor cell H score 115 and Low CPS 1 (
90% reduction in risk of death (HR = 0.1, 95% CI 0.01-0.89, p=0.013) and 81% reduction in the risk of progression or death (HR = 0.19, 95% CI 0.04-1.02, p=0.033)
Prolongation of 4 months in OS and 2 months in PFS
"The identification of CEACAM1 as a potential biomarker, both in serum and at the tumor, corresponds with the multi-faceted function of CEACAM1, as part of the neutrophil extracellular trap (NET) structure affecting NET-related tumor immune evasion, metastasis and other cancer-associated complications, such as thrombosis, at the level of the whole body, as well as modulation of the tumor microenvironment (TME)," stated Purple Biotech VP of Research and Development, Dr. Hadas Reuveni. "Targeting CEACAM1 by CM24 suggests a potential new approach that may address tumor-associated mechanisms affecting the patient at the levels of the tumor, the TME and the whole body. The biomarker data accumulated in this clinical study may help us to direct the treatment of patients who might have a higher chance to benefit from the treatment and could expand our understanding of CEACAM1 and NETs in cancer biology."
Final conclusions from the study:
The combination of CM24, nivolumab, and Nal-IRI/5FU/LV chemotherapy was well tolerated and
demonstrated quantitative improvement in all efficacy parameters, including OS, PFS, ORR and CA19-9, in previously treated PDAC patients.
Based on post-hoc analyses – serum CEACAM1 and MPO, a NET marker, are demonstrated as potential predictive biomarkers for CM24-based therapy, consistent with its mechanism of action (MoA) in targeting CEACAM1 to modulate immune evasion and NET activities.
Results imply that both serum and tumor CEACAM1 levels are potential predictive biomarkers for CM24 based therapy, suggesting multifaceted MoA and the crosstalk of the tumor with the TME and the whole body.
Improved outcome in patients with high tumor CEACAM1 expression and low PD-L1 CPS further support the mechanistic rationale of the CM24/nivolumab combination and highlight its potential in disease settings where immuno-oncology is less effective.
"The design of the randomized trial enabled us to evaluate the benefit of CM24 and nivolumab in combination with standard of care chemotherapy and to analyze potential biomarker data to better prepare for the next study." stated Purple Biotech Head of Clinical and Regulatory Affairs, Dr. Michael Schickler. "We currently expect the design of the next Phase 2b study to include an additional group testing CM24 alone in combination with standard of care with patients selected based on the identified biomarkers, potentially in indications such as gastric and/or biliary tract cancer, in addition to PDAC."
The poster will be available at the Publication section on Purple Biotech’s website following its presentation at the conference.