Topline Results of Phase 3 Trial Show Zanubrutinib Achieves Superior PFS Results Over Ibrutinib in CLL

BeiGene has announced positive topline final progression-free survival (PFS) results from the phase 3 ALPINE trial, which compared zanubrutinib with ibrutinib in patients with chronic lymphocytic leukemia (CLL).

Wednesday’s announcement from the company stated the results were assessed by an independent review committee (IRC) and an investigator. Zanubrutinib, which is sold as Brukinsa, was generally well tolerated, and safety results were consistent with prior findings.

ALPINE is a randomized, global phase 3 trial (NCT03734016) involving 652 patients with previously treated CLL or small lymphocytic lymphoma (SLL). Patients were randomized to receive either zanubrutinib, a second-generation Bruton tyrosine kinase (BTK) inhibitor, or ibrutinib, a first-generation BTK inhibitor sold as Imbruvica. The primary end point was overall response rate (ORR) defined by prespecified noninferiority of zanubrutinib vs ibrutinib, as assessed by the investigator and the IRC. Key secondary end points included PFS and event rates of atrial fibrillation and flutter; other secondary end points include duration of response, overall survival, and the number of adverse events.

“This positive result adds to the growing body of evidence underpinning our belief in the potential for Brukinsa to provide new hope for CLL patients facing this intractable disease. With this final PFS analysis, Brukinsa has achieved superior progression free survival, as well as superiority in overall response rate versus ibrutinib,” Mehrdad Mobasher, MD, MPH, chief medical officer, hematology, for BeiGene, said in a statement. “We look forward to sharing the full results with the medical and patient communities and will submit for presentation at a medical congress and for publication.”

BeiGene awaits word on an indication for zanubrutinib in CLL/SLL but has already received superior placement on the clinical guidelines from the National Comprehensive Cancer Network based on its reduced toxicity.