Acalabrutinib Receives FDA Priority Review in Frontline MCL

Microscopic, photorealistic image of lymphoma cells - Generated with Adobe Firefly

• The FDA granted the supplemental new drug application (sNDA) of acalabrutinib (Calquence) priority review.
• The indication is for the treatment of patients with previously untreated mantle cell lymphoma (MCL).
• The Prescription Drug User Fee Act (PDUFA) target action date is in the first quarter of 2025.

The sNDA of the Bruton tyrosine kinase (BTK) inhibitor acalabrutinib in patients with previously untreated MCL has been granted FDA priority review with a PDUFA target action date of Q1 2025.¹

“Today’s priority review acceptance reinforces the potential of [acalabrutinib] to transform outcomes in untreated mantle cell lymphoma. Data from the ECHO trial [NCT02972840] showed [acalabrutinib] plus chemoimmunotherapy significantly delayed disease progression and showed a trend to improved survival in patients with this currently incurable blood cancer. We are working closely with the FDA to provide patients this potential new treatment as soon as possible,” Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, said in a press release.

Findings from the ECHO trial were presented at the 2024 European Hematology Association Hybrid Congress. Here, acalabrutinib plus bendamustine and rituximab (Rituxan; BR) reduced the risk of disease progression or death by 27% vs BR alone (HR, 0.73; 95% CI, 0.57-0.94; P =.016). Further, adding acalabrutinib led to nearly 1.5 years of additional median progression-free survival (PFS) with a median PFS of 66.4 months with acalabrutinib plus BR and 49.6 months with BR alone.

There was a favorable overall survival (OS) trend observed with acalabrutinib plus BR vs BR alone (HR, 0.86; 95% CI, 0.65-1.13; P =.2743). This trend was sustained; however, most patients in the BR arm who required a subsequent therapy went on to receive a BTK inhibitor, often acalabrutinib. OS data will continue to be assessed as a key secondary end point.

Background of the Phase 3 ECHO Trial

ECHO randomized patients to receive acalabrutinib plus BR (n = 299) or placebo plus BR (n = 299). Acalabrutinib or placebo were administered twice daily orally, bendamustine on days 1 and 2, and rituximab on day 1 for 28-day cycles.²

The study’s primary end point was PFS per independent review committee, and secondary end points included investigator-assessed PFS, overall response rate, OS, duration of response, and time to response.

Patients were eligible for enrollment if they had pathologically confirmed MCL with documentation of a chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers, had not receivedprior systemic anticancer therapies, were 65 years old or younger, and had an ECOG performance status of 2 or lower. Those with significant cardiovascular disease, malabsorption syndrome, or uncontrolled active infection were not eligible for participation.

Acalabrutinib previously received an accelerated approval from the FDA for the treatment of adult patients with MCL following at least 1 prior therapy.³ This accelerated approval is contingent on the results of a confirmatory trial.

REFERENCES:

1. CALQUENCE® (acalabrutinib) granted priority review in the US for patients with untreated mantle cell lymphoma. News release. AstraZeneca. October 3, 2024. Accessed October 3, 2024. https://tinyurl.com/27pn2twc

2. A study of BR alone versus in combination with acalabrutinib in subjects with previously untreated MCL. ClinicalTrials.gov. Updated June 18, 2024. Accessed October 3, 2024. https://clinicaltrials.gov/study/NCT02972840

3. FDA grants accelerated approval to acalabrutinib for mantle cell lymphoma. News release. FDA. October 31, 2017. Accessed October 3, 2024. https://tinyurl.com/4t7yf7cf