BeiGene Presents Initial Phase 1b Data for BTK Inhibitor Zanubrutinib (BGB-3111) Combined with PD-1 Antibody Tislelizumab (BGB-A317) at the 59th American Society of Hematology Annual Meeting
Dec 11, 2017 10:00 AM
“The initial data from this Phase 1b trial indicate that the combination of zanubrutinib and tislelizumab is tolerable with adverse events generally consistent with each therapeutic class. With only a short follow-up time, we have observed objective responses across different malignancy types in this heavily pre-treated population,” commented
“Based on pre-clinical data suggesting the synergy of this combination, we are hopeful that this clinical trial will help to characterize the combination’s potential in treating patients with B-cell malignancies, particularly aggressive lymphomas,” commented
Summary of Results from the Ongoing Phase 1b Trial
The open-label, multi-center Phase 1b trial of zanubrutinib in combination with tislelizumab consists of a dose escalation portion to be followed by a dose expansion portion. Data presented at ASH include patients enrolled at the first two dose levels of the dose escalation phase: dose 1 cohort of zanubrutinib at 320 mg once a day (QD) with tislelizumab at 2 mg/kg every three weeks (Q3W), and dose 2 cohort of zanubrutinib at 320 mg QD with tislelizumab at 5 mg/kg Q3W. Patients in the third dose cohort will receive zanubrutinib at 160 mg twice daily with tislelizumab at 200 mg Q3W.
Among patients with indolent lymphoma, the most common adverse events (AEs) (occurring in ≥ 20% of patients) of any attribution were petechiae/purpura/contusion (31%) and thrombocytopenia (23%). Grade 3-4 AEs of any attribution reported in at least two patients included thrombocytopenia, anemia, and hemolysis (15% each). Besides the two cases of autoimmune hemolysis, there was one more immune-related event, a grade 4 autoimmune encephalitis. The patient was treated with aggressive immunosuppressive therapy and gradually improved over time.
Among patients with aggressive lymphoma, the most common AEs (occurring in ≥ 20% of patients) of any attribution were diarrhea, fatigue, pyrexia, upper respiratory tract infection (33% each), cough (25%), and nausea (25%). Grade 3-4 AEs of any attribution reported in at least two patients included pyrexia (17%). There was one patient with multiple occurrences of grade 2 and 3 pneumonitis.
At the time of data cutoff, the efficacy-evaluable population consisted of 25 patients. The median follow-up time was 5.1 months (0.4-14.1 months). Objective responses were observed in 10 patients (40%). By tumor type, two partial responses (PRs) were observed out of five patients with CLL, one complete response (CR) and one PR were observed out of five patients with FL, one very good partial response and one minor response were observed out of two patients with WM, one CR was observed out of five patients with DLBCL, and three PRs were observed out of five patients with transformed lymphoma.
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of BTK that has demonstrated higher selectivity against BTK than ibrutinib (a BTK inhibitor currently approved by the
Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a 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. Tislelizumab has high affinity and specificity for PD-1. It is differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the encouraging clinical data of zanubrutinib and tislelizumab and our future development plans for zanubrutinib and tislelizumab. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including
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