Dosing of the first patient in a Phase I clinical trial of BGB-3111, a Bruton’s tyrosine kinase (BTK) inhibitor, in combination with BGB-A317, a PD-1 antibody, for the treatment of various B-cell malignancies was initiated earlier this week. This combination study of two internal drug candidates being developed by BeiGene, a clinical-stage biopharmaceutical company focused on developing molecularly targeted and immuno-oncology drugs for the treatment of cancer, follows an ongoing study of another internal combination of BGB-A317 with PARP inhibitor BGB-290.
Bruton’s tyrosine kinase
The trial combines BGB-3111, an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK), which has demonstrated higher selectivity against BTK and higher exposure than ibrutinib, the only BTK inhibitor currently approved by the U.S. Food and Drug Administration and the European Medicines Agency. In addition, available clinical data with BGB-3111 demonstrated sustained 24-hour BTK occupancy in both the blood as well as the lymph node.
Humanized monoclonal antibody
The second drug in the clinical trial combination is BGB-A317, an investigational humanized monoclonal antibody that belongs to a new class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. BGB-A317 has high affinity and specificity for PD-1 and differs from the currently approved PD-1 antibodies with the ability to bind Fc gamma receptor I specifically engineered out.
“We have presented initial clinical data on both of these candidates as single agents,” commented Eric Hedrick, MD, Interim Chief Medical Officer at BeiGene. “We believe the combination of BGB-3111 and BGB-A317 in clinical trials has been well-supported by compelling preclinical data. Additionally, we believe ownership of both components in the combination regimen puts us in an advantageous position to develop the regimen to its full potential.”
The Phase I multi-center, dose escalation and expansion clinical trial of the BGB-3111 and BGB-A317 combination is designed to assess the safety, tolerability, pharmacokinetics, and anti-tumor activities of this combination in patients with B-cell lymphoid malignancies. BGB-3111 will be dosed orally and BGB-A317 will be administered intravenously every three weeks. It is anticipated that about 25 patients will be enrolled into the study.
The trials will be conducted across four centers in Australia.
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