CBP501 is a novel calmodulin-modulating peptide with a well described multimodal anti-tumor mechanism of action.
Even with short time exposure treatment, this mode of action leads to
(a) increased platinum influx into and cytotoxicity to tumor cells specifically,
(b) immunogenic cell death of tumor cells,
(c) suppression of M2 macrophage activity,
(d) reduced populations of cancer stem cells, and
(e) reduced migration/invasion by and epithelial-to-mesenchymal transition (EMT) of tumor cells.
CBP501 also, with cisplatin or carboplatin, enhances the efficacy of several immune checkpoint inhibitors.
In the CT-26 syngeneic mice model, use of CBP501 and a platinum agent with anti-PD1, anti-PDL1 or anti-CTLA4, synergistically suppress tumor growth and increases the CD8 T cell and decreases the M2 macrophage at tumor sites.
For more scientific information about MoA, please see References.
A Phase 1 clinical study using a combination of CBP501 and cisplatin showed the expected safety profile and promising signs of activity in platinum resistant/refractory ovarian cancer patients.
A Phase 2 clinical study achieved the primary efficacy end point, 4 mo. progression-free survival (PFS) rate, for the treatment of chemo-naive malignant pleural mesothelioma with CBP501 in combination with cisplatin and pemetrexed.
A randomized Phase 2 clinical study on the treatment of chemo-naive non-small non-squamous lung cancer led us to find that CBP501 works best in patient populations exhibiting normal WBC before treatment.
This finding also resulted in a new patent for using of this biomarker as part of a criterion for selecting patients for treatment.
A Phase 1b clinical study with the triple drug combination, CBP501, cisplatin and nivolumab, is at the final stage with promising data in heavily pretreated cancer patients, including pancreatic cancer.