AstraZeneca announced that the U.S. Food and Drug Administration has granted approval for Calquence in combination with venetoclax as an all-oral, fixed-duration treatment for adult patients with chronic lymphocytic leukaemia and small lymphocytic lymphoma. The authorization makes this two-drug oral regimen the first of its kind approved for a defined course of therapy in these patient populations.
The regulatory decision is based on findings from the AMPLIFY Phase III trial, data from which were presented at the American Society of Hematology 2024 Annual Meeting and published in The New England Journal of Medicine. The trial compared the Calquence-plus-venetoclax combination against standard-of-care chemoimmunotherapy.
Key efficacy outcomes reported from AMPLIFY include:
- At three years, 77% of patients receiving the Calquence and venetoclax regimen remained progression-free versus 67% for those treated with chemoimmunotherapy.
- Median progression-free survival for the Calquence combination was not reached within the follow-up period, compared with 47.6 months for the chemoimmunotherapy arm.
- The combination reduced the risk of disease progression or death by 35% relative to chemoimmunotherapy, reflected by a hazard ratio of 0.65 (95% confidence interval: 0.49-0.87) and a p-value of 0.0038.
Treatment with Calquence plus venetoclax in the trial was delivered over a fixed duration of 14 cycles, with each cycle lasting 28 days. By contrast, the chemoimmunotherapy comparator was given for six cycles. The fixed-duration oral approach represents a distinct dosing paradigm compared with the multi-cycle chemoimmunotherapy regimen used as the control in AMPLIFY.
Safety observations were consistent with the known profile of Calquence; the trial did not identify any new safety signals associated with the drug when used in combination with venetoclax. The announcement noted tolerability aligned with prior expectations.
Regulatory context included prior authorizations for the Calquence plus venetoclax combination in the European Union, Canada, the UK and several other countries. Applications grounded in the AMPLIFY results remain under review in additional jurisdictions.
The AMPLIFY study was a randomized, global, multi-centre, open-label Phase III trial that enrolled patients between 2019 and 2021. It included sites across 27 countries spanning North and South America, Europe, Asia and Oceania.
Calquence is described as a second-generation, selective inhibitor of Bruton’s tyrosine kinase. The molecule binds covalently to the enzyme, inhibiting its activity as part of its mechanism of action.
Chronic lymphocytic leukaemia is the most common leukaemia in adults. The article cites an estimate that 18,500 people received first-line treatment for CLL in the United States in 2024.