Final data from a phase 2 study, which evaluated CM24 in patients with pancreatic cancer who possessed CEACAM1 biomarkers, showed that the combination of CM24, Opdivo (nivolumab) and Nal-IRI/5FU/LV chemotherapy was well tolerated, according to a news release from Purple Biotech.
Data findings will be presented at the Annual Meeting of the American Association of Cancer Research (AACR) 2025.
The presentation will cover a randomized, controlled phase 2 study that showed proof of concept in 31 patients with advanced or metastatic pancreatic ductal adenocarcinoma after first-line therapy, comparing CM24 plus Opdivo and chemotherapy versus chemotherapy alone.
Glossary:
CEACAM1: a protein found in the blood and some tumors that may help predict how well a treatment will work.
CM24: an experimental drug being studied to help the immune system fight cancer by targeting CEACAM1.
NET (neutrophil extracellular trap): web-like structures released by certain white blood cells that can affect how cancer grows and spreads.
MPO (myeloperoxidase): a substance linked to NETs that may also help predict how well a treatment works.
PD-L1 combined positive score (CPS): a lab test that measures how much of the PD-L1 protein is found in tumor and immune cells, which may predict response to some immunotherapies.
Tumor microenvironment (TME): the area around a tumor, including blood vessels, immune cells and other tissues, which can affect how a tumor grows and responds to treatment.
A 78% reduction in risk of death and 81% reduction in risk of progression or death were observed in patients with defined pretreatment ranges of serum or tumor CEACAM1. A 61% reduction in risk of death and 72% reduction in risk of progression or death were seen in those with defined pretreatment ranges of serum CEACAM1 or myeloperoxidase. In patients with high tumor CEACAM1 and low PD-L1 combined positive score, a 90% reduction in risk of death and 81% reduction in risk of progression or death were reported.
The biomarkers identified in the phase 2 study are planned for use in patient selection for the upcoming phase 2b study.
“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,” Purple Biotech CEO Gil Efron, stated in the news release. “The new, previously unpublished data presented at AACR demonstrate significant overall survival and progression-free survival benefit for patients meeting the criteria of either serum CEACAM1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.”
Additionally, the median progression-free survival was prolonged by 1.9 months in the experimental arm versus the control arm. In biomarker-defined subgroups, progression-free survival was prolonged by 2.9 months in patients with pre-treatment CEACAM1 expression and by 2.2 months in those with defined CEACAM1 or myeloperoxidase (MPO) serum levels. Among patients with high CEACAM1 tumor cell H score and low PD-L1 CPS, progression-free survival was prolonged by 2 months.
Post-hoc analyses showed that serum CEACAM1 and MPO, a neutrophil extracellular trap (NET) marker, may serve as predictive biomarkers for CM24-based therapy, aligning with its mechanism of targeting CEACAM1 to modulate immune evasion and NET activity, as per the release.
Findings suggest both serum and tumor CEACAM1 levels could predict response to CM24, reflecting its multifaceted mechanism and interaction with the tumor microenvironment and systemic biology. In addition, improved outcomes in patients with high tumor CEACAM1 expression and low PD-L1 CPS further support the rationale for the CM24 and Opdivo combination, particularly in settings where immunotherapy is less effective.
“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 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)," Purple Biotech VP of research and development, Dr. Hadas Reuveni, said in the news release.
He continues, "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 [tumor microenvironment] 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.”
For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.
