Acalabrutinib/Venetoclax Shows PFS Improvements in Previously Untreated CLL

Microscopic image of CLL cells - Generated with Google Gemini AI

In patients with previously untreated chronic lymphocytic leukemia (CLL), fixed-duration acalabrutinib (Calquence) plus venetoclax (Venclexta), with or without obinutuzumab (Gazvya) led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs standard-of-care chemotherapy, according to findings from the phase 3 AMPLIFY trial (NCT03836261).¹

A positive trend in overall survival (OS) was also observed in the acalabrutinib/venetoclax arm with or without obinutuzumab.

“The AMPLIFY results demonstrate the potential of acalabrutinib and venetoclax with or without obinutuzumab to be effective and well-tolerated fixed-duration treatment options for patients with chronic lymphocytic leukemia. This is an important advance in this setting as fixed-duration regimens allow those living with this chronic disease to take breaks from their treatment, thereby decreasing the possibility of long-term adverse events and drug resistance and improving quality of life,” Jennifer R. Brown, MD, PhD, director of the CLL Center of the Division of Hematologic Malignancies at the Dana-Farber Cancer Institute and principal investigator of the trial, said in a press release.

Safety and tolerability were consistent with the known profiles of the agents, and no new safety signals were identified. Full data from this interim analysis will be presented at an upcoming medical meeting and shared with regulatory authorities.

“The progression-free survival and overall survival results from the AMPLIFY phase 3 trial demonstrate the potential of including a [Bruton tyrosine kinase (BTK)] inhibitor in a fixed-duration regimen and reinforce our leadership in advancing science for patients with chronic lymphocytic leukemia. If approved, [acalabrutinib] would become the only second-generation BTK inhibitor available as both a treat-to-progression and fixed-duration treatment, providing more options for patients and their healthcare providers,” said Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, in a press release.

About the Phase 3 AMPLIFY Trial

The phase 3, randomized, global, multicenter, open-label AMPLIFY trial is evaluating acalabrutinib plus venetoclax with and without obinutuzumab vs chemoimmunotherapy in 984 patients across 171 locations with previously untreated CLL without a 17p deletion or TP53 mutation.²

The study’s primary end point is PFS, and secondary end points include OS, event-free survival, overall response rate, duration of response, and time to next treatment.¹

Patients were randomized 1:1:1 to receive acalabrutinib/venetoclax with obinutuzumab, acalabrutinib/venetoclax without obinutuzumab, or investigator’s choice of either fludarabine, cyclophosphamide, and rituximab (Rituxan) or bendamustine and rituximab.²

Patients aged 18 and older with an ECOG performance status of 0 to 2 were eligible for enrollment in the study. Those who had received prior CLL-specific therapies, had a transformation of CLL to an aggressive non-Hodgkin lymphoma, had central nervous system involvement, had significant cardiovascular disease, or had known bleeding disorders were not eligible for participation in the study.

The study enrolled patients from 2019 to 2021 and has an estimated completion date of January 6, 2027.

REFERENCES:

1. Fixed-duration Calquence plus venetoclax, with or without obinutuzumab, significantly improved progression-free survival in 1st-line chronic lymphocytic leukaemia in AMPLIFY phase III trial. News release. AstraZeneca. July 29, 2024. Accessed July 29, 2024. https://tinyurl.com/yu4jernz

2. Study of acalabrutinib (ACP-196) in combination with venetoclax (ABT-199) with and without obinutuzumab (GA101) versus chemoimmunotherapy for previously untreated CLL (AMPLIFY). ClinicalTrials.gov. Updated May 29, 2024. Accessed July 29, 2024. https://clinicaltrials.gov/study/NCT03836261