Date: 2015-09-21
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival.
Company: BergenBio (Norway)
Product: BGB324 in combination with immune checkpoint inhibitors
Action
mechanism: AXL inhibitor/ receptor tyrosine kinase inhibitor/monoclonal antibody/immune checkpoint inhibitor. BGB324 is a highly selective, oral AXL inhibitor that blocks the epithelial-mesenchymal transition, which is a key driver of metastasis and drug-resistance.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On September 21, 2015, BerGenBio has announced new preclinical data on lead compound, BGB324, in combination with immune checkpoint inhibitors, has been presented as a poster (“BGB324, a selective small molecule inhibitor of the receptor tyrosine kinase Axl, enhances immune checkpoint inhibitor efficacy”) at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival. This preclinical data highlights that BGB324, a first-in-class, highly selective small molecule inhibitor of the Axl receptor tyrosine kinase, used in combination with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1) in mouse carcinoma models showed enhanced tumour clearance, survival and tumour infiltration of cytotoxic T lymphocytes compared with checkpoint inhibition alone. The studies were conducted in an aggressive mammary adenocarcinoma (4T1) syngeneic mouse model. BGB324 (50 mg/kg bid) significantly enhanced responsiveness to anti-CTLA-4/anti-PD-1 treatment (10 mg/kg of each, 4 doses) in Balb/C mice bearing established 4T1 tumours. The well-tolerated combination of BGB324 + anti-CTLA-4/anti-PD-1 resulted in durable primary tumour clearance in 23% of treated mice versus 5.6% obtained with anti-CTLA-4/anti-PD-1 alone (p=0.0157). In a separate study, BGB324 + anti-CTLA-4 treated resulted in 22% long-term primary tumour clearance while no response was observed with anti-CTLA4 treatment alone. The extensive metastasis to the lung, liver and spleen characteristic of this model were concomitantly abrogated in the animals responding to the combination treatment. In addition, BGB324 + anti-CTLA-4/anti-PD-1 treated tumours displayed enhanced infiltration of cytotoxic T lymphocytes. Importantly, responding animals rejected orthotopic 4T1 tumor cell re-challenge, demonstrating sustained tumour immunity.
