AstraZeneca targets first-line mantle cell lymphoma therapy with Phase III data


AstraZeneca targets first-line mantle cell lymphoma therapy with Phase III data

Published: May 03, 2024

By Tristan Manalac


AstraZeneca on Thursday revealed high-level results from the Phase III ECHO trial, demonstrating that BTK inhibitor Calquence (acalabrutinib)—when used with standard chemotherapy agents bendamustine and rituximab—yielded significant survival benefits as a first-line therapy in mantle cell lymphoma.

The pharma did not provide specific data in its announcement but said that the Calquence-based regimen resulted in a “statistically significant and clinically meaningful improvement” in progression-free survival, compared with standard of care. ECHO, a randomized, double-blinded and placebo-controlled trial, enrolled nearly 600 patients with previously untreated mantle cell lymphoma (MCL).

Data for overall survival (OS) was not yet mature at the time of the interim analysis, but AstraZeneca noted in its announcement that “a trend was observed in favor of Calquence plus chemoimmunotherapy.” ECHO will continue as planned to assess OS.

In terms of safety, ECHO found no new signals of concern. Calquence’s adverse event profile in the study was consistent with what has been established in prior trials.

Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, in a statement called the results “impactful” and said that “bringing Calquence to the first-line setting significantly delays disease progress and, for the first time, shows potential to extend survival.”

AstraZeneca will present full data and analyses from ECHO at an upcoming medical congress and will share these with regulatory authorities.

Designed to be orally available, Calquence is a small-molecule BTK inhibitor that works by covalently bonding to the active site of the BTK protein, which deactivates its enzymatic activity. BTK is a signaling molecule involved in the pathways for B-cell proliferation and trafficking, and its inhibition could prevent the division and survival of malignant B-cells.

The FDA first approved Calquence in 2017 for previously treated MCL and the drug has since become one of AstraZeneca’s top-performing assets. In the first quarter of 2024, Calquence brought in $718 million for the pharma, up 6% from its sales during the same period in 2023.

AstraZeneca is also assessing Calquence as a monotherapy for several B-cell blood cancers, including chronic lymphocytic leukemia and diffuse large B-cell lymphoma. In addition, the pharma is studying various Calquence-based combination regimens.

Thursday’s late-stage readout comes a year after AbbVie and J&J voluntarily pulled the accelerated MCL approval for their BTK blocker Imbruvica (ibrutinib). While data from Phase III confirmatory trials showed that Imbruvica can significantly improve PFS versus placebo, the treatment yielded no significant benefit in terms of OS and complete response.

Source: BioSpace