Zanubrutinib Produces Improved Survival Compared with Ibrutinib in Final PFS Analysis for Relapsed/Refractory CLL

Zanubrutinib (Brukinsa) demonstrated a superior progression-free survival (PFS) vs ibrutinib (Imbruvica) as a treatment for patients with relapsed/refractory chronic lymphocytic leukemia (CLL), according to a recent press release from BeiGene on topline results from the final PFS analysis of the randomized, international phase 3 APLINE trial (NCT03734016).¹

The analysis was conducted via independent review committee and investigator assessment. Further data regarding other key end points of the trial will be detailed at a future scientific presentation.

“This positive result adds to the growing body of evidence underpinning our belief in the potential for [zanubrutinib] to provide new hope for [patients with] CLL facing this intractable disease. With this final PFS analysis, [zanubrutinib] has achieved superior progression-free survival, as well as superiority in overall response rate (ORR) versus ibrutinib,” Mehrdad Mobasher, MD, MPH, chief medical officer of hematology at BeiGene, said in the press release. “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.”

The global phase 3 ALPINE trial was designed to assess the efficacy of zanubrutinib compared with ibrutinib among a total of 652 enrolled patients previously treated for relapsed or refractory CLL or small lymphocytic leukemia (SLL). Patients were randomly assigned 1:1 to either receive 160 mg of oral zanubrutinib twice a day or 420 mg of oral ibrutinib once a day. Treatment for patients continued until disease progression or unacceptable toxicity.

Adult patients with a confirmed diagnosis of CLL or SLL based on 2008 iwCLL criteria were eligible to participate in the trial if they had relapsed on or were refractory to at least 1 previous systemic therapy for CLL or SLL. Further inclusion criteria included a measurable disease by a CT or MRI; an ECOG performance status of 0 to 2; a life expectancy of at least 6 months; and adequate bone marrow, renal, and hepatic function. Patients were excluded from the trial if they had a known history of prolymphocytic leukemia or history of or currently suspected Richter’s transformation, clinically significant cardiovascular disease, and previous malignancy within the past 3 years.

The primary end point of the ALPINE trial is overall response rate (ORR) determined by investigator assessment for up to 50 months, with secondary end points including PFS, duration of response, and the incidence of adverse effects (AEs).

Investigators of the ALPINE trial had previously announced positive ORR findings in April 2022.² In the response analysis, zanubrutinib produced an ORR of 80.4% compared with 72.9% among patients receiving ibrutinib (2-sided P = .0264) with a median follow-up of 24.2 months.

The safety findings associated with the PFS analysis were consistent with previous reports and indicated that zanubrutinib was tolerated among patients. The most frequently observed grade 3 or higher AEs reported during the response analysis for zanubrutinib and ibrutinib, respectively, were neutropenia (14.2% vs. 13.9%), hypertension (12.7% vs. 10.2%), pneumonia (4.0% vs. 7.4%), neutrophil count decreases (4.3% vs. 4.0%), and COVID-19 pneumonia (4.3% vs. 3.1%).

References

1. BeiGene announces positive topline results from final progression-free survival analysis of BRUKINSA® (zanubrutinib) compared to IMBRUVICA® (ibrutinib) in phase 3 chronic lymphocytic leukemia (CLL) trial. News release. BeiGene. October 12, 2022. Accessed October 13, 2022. https://bit.ly/3RZciqz
2. 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. April 11, 2022. Accessed October 13, 2022. https://bit.ly/3CUN4Fu