As AbbVie and Johnson & Johnson’s Imbruvica retreated, AstraZeneca’s Calquence has become the first BTK inhibitor to claim a unique win in previously untreated mantle cell lymphoma (MCL).
Calquence, used in combination with bendamustine and rituximab (BR), significantly staved off cancer progression or death compared with the standard chemoimmunotherapy alone in newly diagnosed MCL, AstraZeneca said Thursday.
The result came from an interim analysis of a phase 3 trial called ECHO, for which AZ most recently projected a readout in 2025.
Data from ECHO could potentially help Calquence convert its existing accelerated approval in previously treated MCL into a full nod. But a big question remains whether AZ can immediately file with the FDA, especially given the bad precedent of Imbruvica.
The ECHO readout clearly arrived earlier than AZ had expected. The trial bears a primary completion date in October 2025. Although the trial met its primary endpoint of progression-free survival, the FDA has in the past asked other drugs for more mature overall survival data before an application can be submitted.
For now, AZ has reported a positive life extension trend in favor of the Calquence combo, but the patient survival data were still not mature at the time of the analysis. The study will continue to assess that key secondary endpoint.
In a Thursday statement, AZ’s oncology R&D chief, Susan Galbraith, Ph.D., highlighted the early overall survival signal was the first for a BTK inhibitor. She also touted Calquence’s “differentiated safety profile,” alongside the tumor progression win.
In response to a Fierce Pharma inquiry, an AZ spokesperson said the data will be shared with health authorities and that the trial remains ongoing.
AZ’s success came a year after AbbVie and J&J decided to pull Imbruvica’s accelerated approval in previously treated MCL and marginal zone lymphoma. It was exactly overall survival data that tripped up Imbruvica’s MCL indication.
In the phase 3 SHINE study in first-line MCL, Imburvica’s combination with BR significantly slashed the risk of disease progression or death by 25% compared with BR alone. However, overall survival was similar in the two arms, as the Imbruvica regimen was linked to a marginal 7% increased risk of death.
Even though Imbruvica is out of the picture, Calquence might still face competition in the form of BeiGene’s Brukinsa in first-line MCL in the future. Brukinsa, which also has an FDA accelerated approval in previously treated MCL, is being evaluated alongside rituximab alone versus the BR combo in untreated MCL in the phase 3 BGB-3111-306 trial.
The BeiGene trial finished recruitment at the beginning of 2024 and bears a primary completion date in March 2027, according to ClinicalTrials.gov.
Brukinsa and Calquence are locked in a new round of rivalry, as first-to-market Imbruvica lost the favor of increasingly more doctors in part because of its safety profile.
In 2023, BeiGene recorded $1.3 billion in global Brukinsa sales, which marked a 129% jump year over year. During the same period, Calquence brought AZ $2.5 billion sales after a 22% increase.
In the all-important first-line chronic lymphocytic leukemia (CLL) setting, Calquence remained the leading BTK inhibitor across the U.S. and Europe, according to AZ. A few days ago, the company read out the phase 3 ChangE trial in Asia showing Calquence monotherapy beat the combination of chlorambucil and rituximab on PFS in untreated CLL.
Meanwhile, the phase 3 AMPLIFY trial is pairing Calquence with AbbVie and Roche’s BCL2 inhibitor Venclexta with or without Roche’s anti-CD20 antibody Gazyva in first-line CLL. Similarly, BeiGene is combining Brukinsa with its own second-generation BCL2 inhibitor sonrotoclax in CLL.
Editor's Note: The story has been updated to reflect that the phase 3 ChangE trial for Calquence has already read out.