The global Phase 3 trial evaluating BeiGene’s investigational Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib in chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) has started dosing patients.
The study (NCT03734016) is recruiting patients who failed to respond (refractory) or whose disease returned after responding to prior therapies (relapsed), and is expected to include 400 patients across 150 clinical sites in the U.S., China, Europe, Australia, and New Zealand.
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.
In a Phase 2 trial (NCT03206918) zanubrutinib showed promising results, shrinking the tumors of 80% of CLL/SLL patients who had received at least one prior therapy. Responses were also long-lasting, as more than half of patients were responding to treatment after a median follow-up of 9.1 months.
The findings led BeiGene to ask that zanubrutinib be approved in China for relapsed or refractory CLL/SLL patients.
The ongoing Phase 3 trial will now confirm the benefits of zanubrutinib in these patients, comparing the approach with another BTK inhibitor — Imbruvica (ibrutinib) — approved for CLL/SLL patients who received prior treatment.
In the trial, patients will be randomly assigned twice-daily zanubrutinib (160 mg) or once-daily Imbruvica (420 mg), both given orally.
The primary goal of this Phase 3 trial is to see whether more patients respond to zanubrutinib than to Imbruvica. Secondary measures include the time patients live without disease worsening, duration of response, overall survival, patient-reported outcomes, and safety.
“We continue to be encouraged by data on zanubrutinib in various B-cell malignancies and are excited to further expand the development program for zanubrutinib in CLL and SLL with this Phase 3 trial, which represents the second Phase 3 study directly comparing zanubrutinib to ibrutinib,” Jane Huang, MD, chief medical officer, hematology, at BeiGene, said in a press release.
In addition to CLL/SLL, zanubrutinib has shown high response rates in several other B-cell lymphomas, including Waldenström macroglobulinemia, mantle cell lymphoma, marginal zone lymphoma, and follicular lymphoma.
Currently, the medicine is being tested in a broad global program. It includes a Phase 3 trial (NCT03053440) for patients with Waldenström macroglobulinemia, a Phase 3 trial (NCT03336333) for previously untreated CLL/SLL patients, and an open-label Phase 2 trial (NCT03520920) for patients with relapsed or refractory follicular lymphoma.
The therapy has also received fast track designation by the U.S. Food and Drug Administration (FDA) for patients with Waldenström macroglobulinemia and is being reviewed in China as a potential treatment for mantle cell lymphoma.