Acalabrutinib Demonstrates Improvements in PFS in Patients With Previously Untreated MCL

Author(s):

Gillian McGovern, Assistant Editor

Compared with placebo, acalabrutinib plus standard of care chemoimmunotherapy demonstrated better progression-free survival in patients with mantle cell lymphoma.

Image credit: David A Litman | stock.adobe.com

About the Trial

Trial Name: A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL

ClinicalTrials.gov ID: NCT02972840

Sponsor: Acerta Pharma BV

Completion Date (Estimated): October 28, 2025

In positive interim analysis results from the phase 3 trial ECHO (NCT02972840), acalabrutinib (Calquence; AstraZeneca) in combination with standard of care chemoimmunotherapy—bendamustine and rituximab—demonstrated both statistically significant and clinically meaningful improvement in progression-free survival (PFS) in adult patients with previously untreated mantle cell lymphoma (MCL) compared with standard of care alone.¹

Acalabrutinib is a next-generation, selective inhibitor of Bruton tyrosine kinase (BTK) that binds covalently to BTK to hinder its activity. BTK signaling results in the activation of pathways that are necessary for B-cell proliferation, trafficking, chemotaxis, an adhesion within B cells. In November 2019, acalabrutinib was granted a supplemental approval for the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia. Prior to this, acalabrutinib was also granted an accelerated approval for mantle cell lymphoma.^1,2

ECHO is a randomized, double-blind, placebo-controlled, multicenter phase 3 trial that is evaluating the safety and efficacy of acalabrutinib plus bendamustine and rituximab compared with standard of care chemoimmunotherapy alone. A total of 598 adult patients aged 65 years or older with previously untreated CML were enrolled in the study. The trial’s primary end point is PFS, and key secondary end points include OS, overall response rate (ORR), duration of response (DoR), and time to response (TTR).^1,3

The participants were randomly assigned to receive either twice-daily oral acalabrutinib plus intravenous (IV) bendamustine (administered days 1 and 2) and rituximab (administered day 1) or placebo plus bendamustine and rituximab at the same doses and frequencies during 28-day cycles. Following 6 cycles of the acalabrutinib or placebo regimens, patients will receive acalabrutinib or placebo plus maintenance rituximab for 2 years and then either acalabrutinib or placebo only until disease progression.^1,3

“These positive PFS results from the ECHO phase 3 trial could provide a new standard of care for patients with MCL. Incorporating [acalabrutinib] into the first-line MCL setting would give many more patients the opportunity to benefit from the robust efficacy and strong safety profile we’ve seen with this medicine,” said principal investigator Michael Wang, MD, professor, Puddin Clarke Endowed, director of Mantle Cell Lymphoma Program of Excellence, and co-director of clinical trials at MD Anderson Cancer Center in Houston, Texas, in a press release.¹

Additionally, acalabrutinib demonstrated safety and tolerability consistent with previously known profiles, with no safety signals observed. OS data were not mature at the time of the analysis, and the trial will continue to assess for it.¹

In the phase 3 ELEVATE-TN trial (NCT02475681), acalabrutinib demonstrated superior benefits and positive safety and tolerability profiles in PFS vs chlorambucil plus obinutuzumab in patients with previously untreated CLL. Additionally, the treatment also demonstrated longer OS. Further, in the phase 3 ASCEND trial (NCT02970318), acalabrutinib monotherapy showed statistically significant and clinically meaningful improvement in PFS. The most common adverse events observed in the trials were anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain.^2,4

“These impactful results [in the ECHO trial] in MCL show that bringing [acalabrutinib] to the first line setting significantly delays disease progression and, for the first time, shows potential to extend survival," said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in the press release. "The improvement in PFS together with the differentiated safety profile of [acalabrutinib] are both important as we strive to transform outcomes earlier in the course of disease treatment.”¹

References

1. AstraZeneca. Calquence combination regimen demonstrated statistically significant and clinically meaningful improvement in progression-free survival in 1st-line mantle cell lymphoma in ECHO Phase III trial. News release. May 2, 2024. Accessed May 7, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/calquence-combination-improved-pfs-in-1l-mcl.html

2. Barrett, J. FDA Approves Acalabrutinib for CLL Indication. Pharmacy Times. November 21, 2019. Accessed May 7, 2024. https://www.pharmacytimes.com/view/fda-approves-acalabrutinib-for-cll-indication

3. A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL.ClinicalTrials.gov identifier: NCT02972840. Updated March 8, 2024. Accessed <ay 7, 2024. https://clinicaltrials.gov/study/NCT02972840

4. Mollison, C. Calquence Demonstrates Sustained Survival Benefit for CLL. Pharmacy Times. June 5, 2022. Accessed May 7, 2024. https://www.pharmacytimes.com/view/calquence-demonstrates-sustained-survival-benefit-for-cll