BeiGene‘s investigational zanubrutinib is showing promising response rates, ranging from 42% to 100%, in several B-cell lymphoma subtypes, preliminary data from a Chinese Phase 1 trial show. Treatment was also well-tolerated.
Jun Zhu, MD, medical department chief at the Beijing Cancer Hospital, presented the preliminary data at the 21st Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) this September in Xiamen, China.
“These preliminary safety, tolerability and pharmacokinetics data of zanubrutinib support its ongoing clinical study. In this study, the preliminary results suggest zanubrutinib has a high rate of activity and is generally well-tolerated, which we believe is based on its potency and high degree of selectivity,” Jun said in a press release.
The Bruton’s tyrosine kinase, or BTK, is part of a pathway that helps B-cells stay alive and divide. By targeting BTK, zanubrutinib blocks survival signals in the cancerous B-cells, promoting their death and halting the progression of lymphoma.
The Phase 1 trial recruited patients with B-cell lymphoma, including two patients with Waldenström macroglobulinemia (WM); nine patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); two patients with mantle cell lymphoma (MCL); five with marginal zone lymphoma (MZL); and 26 patients with follicular lymphoma (FL).
The study was conducted in two parts. In part 1, patients received escalating doses of oral zanubrutinib to determine the best dose for further testing — called the recommended Phase 2 dose. Then, patients were included in the expansion portion, where they received the optimal dose — 160 mg zanubrutinib, twice daily.
In total, the trial recruited 44 patients — 21 to the dose-escalation phase and 23 to the dose-expansion phase.
Preliminary data had shown that zanubrutinib’s pharmacokinetics — how it is absorbed, distributed, metabolized, and eliminated from the body — were similar among Chinese and non-Chinese patients. Moreover, the therapy was effective at targeting BTK after single or multiple doses.
After a median follow-up of 9.5 months, a total of 21 patients out of the initial 44 were still on treatment. At this point, 34 patients were evaluable for response.
The data showed that all patients with CLL/SLL responded to treatment, including two complete responses, six partial responses, and one partial response with lymphocytosis (an increase in the number of white blood cells, also called lymphocytes).
Among the two MCL patients, one showed a complete response and one had stable disease. For those with WM patients, one had a partial response and the other stable disease.
A 42% overall response rate was seen in the patients with FL, with two and nine patients experiencing complete and partial responses, respectively.
Out of the five patients with MZL, three had stable disease and no data was available for the other two patients.
The therapy was well-tolerated at all tested doses, without any signs of toxicity, and no deaths due to adverse events have been registered.
The most common adverse events included a decrease in the number of neutrophils (seen in half of patients) and anemia (32%). Additional adverse outcomes included upper respiratory tract infections (25%), drop in the number of white blood cells (25%) and platelets (23%), as well as rash (23%), presence of red blood cells in the urine, (20%), and an excess of uric acid in the blood (20%).
“We continue to be encouraged by clinical data on zanubrutinib, including these results, which we believe support its broad global clinical development,” said Jane Huang, MD, chief medical officer, Hematology, at BeiGene.
Zanubrutinib is being reviewed for the treatment of mantle cell lymphoma patients in China who failed prior therapies.
“We are hopeful that it will give patients in China, and across the world, a new treatment option where it is so greatly needed,” Huang said.
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