First Response Analysis of ALPINE Trial Shows Superior ORR With Zanubrutinib Vs Ibrutinib in CLL

Zanubrutinib (Brukinsa) demonstrated superiority over ibrutinib (Imbruvica) in terms of overall response rate (ORR) per independent review committee (IRC) assessment in adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to data from the final response analysis of the phase 3 ALPINE trial (NCT03734016).¹

At median follow-up of 24.2 months, zanubrutinib elicited an ORR of 80.4% compared with 72.9% with ibrutinib in this population (2-sided P = .0264). The agent was also found to be generally well tolerated, with observations consistent with what has previously been reported with the agent.

“We are pleased to announce updated topline data from the phase 3 ALPINE trial for [zanubrutinib], which demonstrated a superior ORR vs ibrutinib in CLL patients who have seen their disease return or spread after prior therapy,” Lai Wang, PhD, global head of research and development at BeiGene, Ltd., stated in a press release. “We understand that for people living with CLL and their families, relapse and treatment resistance are especially devastating. That’s why we are encouraged by this final response analysis, which adds to the growing body of clinical evidence for [zanubrutinib] as a potential treatment for CLL.”

ALPINE enrolled patients with relapsed or refractory CLL or SLL who previously received at least 1 systemic therapy. A total of 652 patients were recruited, and 415 patients were randomized to receive either zanubrutinib at 160 mg twice daily (n = 207) or ibrutinib at 420 mg once daily (n = 208).

The primary end point of the study was ORR per investigator assessment. Additional end points of interest included duration of response (DOR), progression-free survival (PFS), and overall survival (OS), atrial fibrillation of any grade, patient-reported outcomes, and safety.

Baseline characteristics were found to be well balanced between the 2 treatment arms. The median age of those enrolled was 67 years and the majority were male.

Data previously presented during the 2021 EHA Annual Congress showed that at a data cutoff of approximately 12 months, zanubrutinib elicited an ORR of 78.3% (95% CI, 72%-83.7%) vs 62.5% (95% CI, 55.5%-69.1%) with ibrutinib.2 When partial and complete responses, as well as partial response-lymphocytosis, were considered, the ORRs in the investigative and control arms were 88.4% and 81.3%, respectively.

Those who received zanubrutinib also experienced a better 12-month PFS rate compared with those who were given ibrutinib, at 94.9% and 84%, respectively (HR, 0.4; 95% CI, 0.23-0.69; P = .0007). The 12-month OS rates proved to be relatively similar between the investigative and control arms, at 97% and 92.7%, respectively (HR, 0.54; 95% CI, 0.25-1.16; P = .1081).

Data from the prespecified safety analysis had indicated that the rate of atrial fibrillation or flutter was lower with zanubrutinib than with ibrutinib. With a median follow-up of 24.2 months, the rate of atrial fibrillation was 4.6% (n = 15) with zanubrutinib vs 12.0% (n = 39) with ibrutinib.

The most common grade 3 or higher adverse effects experienced by those in the investigative and control arms, respectively, included neutropenia (14.2% vs 13.9%), hypertension (12.7% vs 10.2%), pneumonia (4% vs 7.4%), neutrophil count decreased (4.3% vs 4.0%), and COVID-19 pneumonia (4.3% vs 3.1%).

Thirteen percent of the 324 patients in the zanubrutinib arm discontinued treatment because of toxicity vs 17.6% of the 324 patients in the ibrutinib arm.

Data from ALPINE have been submitted as support for applications seeking the approval of zanubrutinib in patients with CLL in the United States, the European Union, and other markets on a global scale.

In February 2022, the FDA and the European Medicines Agency accepted supplemental new drug applications for zanubrutinib in CLL. The FDA is expected to decide on the application by October 22, 2022.3

References

IRC determines BRUKINSA (zanubrutinib) demonstrates superior overall response rate versus ibrutinib in final response analysis of ALPINE trial in chronic lymphocytic leukemia. News release. BeiGene, Ltd.; April 11, 2022. Accessed April 11, 2022. https://bit.ly/3riEqdA

1. Hillmen P, Eichhorst B, Brown JR, et al. First interim analysis of ALPINE study: Results of a phase 3 randomized study of zanubrutinib vs ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Presented at: 2021 European Hematology Association Congress; June 9-17, 2021; Virtual. Abstract LB190.
2. BeiGene announces US FDA acceptance of supplemental new drug application for BRUKINSA (zanubrutinib) in chronic lymphocytic leukemia. News release. BeiGene; February 22, 2022. Accessed April 11, 2022. https://bit.ly/3s7MBKx