AstraZeneca is seeking a fixed-duration approval for Calquence, which will allow patients with chronic lymphocytic leukemia to take breaks from the therapy and prevent excessive toxicities and drug resistance.
AstraZeneca on Monday released high-level findings from the Phase III AMPLIFY study, demonstrating that a combination regimen of its BTK blocker Calquence (acalabrutinib) with AbbVie and Roche’s Venclexta (venetoclax) improves survival in patients with chronic lymphocytic leukemia.
AMPLIFY, a randomized, global and open-label study, found that the Calquence combo led to a “statistically significant and clinically meaningful improvement” in progression-free survival (PFS), the trial’s primary efficacy endpoint. The trial enrolled previously untreated adult patients and administered the Calquence-Venclexta regimen with or without obinutuzumab. As a control, the late-stage study used investigator’s choice of chemotherapy.
Calquence plus Venclexta also resulted in a favorable trend in overall survival (OS), a key secondary endpoint of the study. OS data were immature at the time of the interim analysis and AMPLIFY continues to evaluate OS.
In terms of safety, the trial found no new signals of concern. Calquence and Venclexta’s respective adverse event profiles in AMPLIFY were consistent with what had been established in previous studies.
Susan Galbraith, AstraZeneca’s executive vice president for oncology R&D, in a statement said that AMPLIFY’s results “demonstrate the potential of including a BTK inhibitor in a fixed-duration regimen” for the treatment of chronic lymphocytic leukemia (CLL).
“If approved, Calquence 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,” Galbraith said.
Designed to be orally administered, Calquence is a small-molecule blocker of the BTK protein, which is a key signaling molecule in the B-cell proliferation, adhesion and trafficking pathways. By disrupting these cascades, Calquence can prevent the proliferation of malignant B-cells and tumor growth, according to its label.
The FDA first approved Calquence in October 2017 for the treatment of mantle cell lymphoma (MCL), and then again in 2019 for CLL or small lymphocytic leukemia. Currently, Calquence is used in CLL until patients experience disease progression or intolerable side effects.
With Monday’s readout, AstraZeneca will seek approval for a “fixed-duration” use of Calquence, which will allow patients to take breaks from the treatment. This could help lower “the possibility of long-term adverse events and drug resistance and improving quality of life,” Jennifer Brown, director of the CLL Center of the Division of Hematologic Malignancies at the Dana-Farber Cancer Institute, said in a statement. Brown has previously disclosed professional relationships with AstraZeneca.
Beyond CLL, AstraZeneca is also continuing Calquence’s development in MCL. In May 2024, the pharma unveiled promising Phase III data in this indication, touting a clinically significant PFS improvement when using Calquence, in combination with standard chemotherapy, in the first-line setting.
