AstraZeneca said that an interim analysis of the AMPLIFY study revealed that a fixed duration of Calquence (acalabrutinib) combined with venetoclax, with or without obinutuzumab, significantly improved progression-free survival (PFS) in chronic lymphocytic leukaemia (CLL).
The Phase III study compared this combination to standard-of-care chemoimmunotherapy in previously untreated patients and demonstrated a statistically significant and clinically meaningful improvement in PFS.
The secondary endpoint analysis showed a positive trend towards improved overall survival (OS) for patients treated with Calquence and venetoclax, with or without obinutuzumab, compared to the standard treatment. However, the OS data remain immature, and further monitoring is needed to fully assess this endpoint, said the company.
The safety profile of the investigational combination therapy was consistent with the known profiles of the individual medications, with no new safety concerns and low rates of cardiac toxicity observed.
Results from the trial are expected to be presented by AstraZeneca at an upcoming medical conference and will be shared with regulatory authorities worldwide.
AstraZeneca oncology R&D executive vice president Susan Galbraith said: “The progression-free survival and overall survival results from the AMPLIFY Phase III trial demonstrate the potential of including a BTK inhibitor in a fixed-duration regimen and reinforce our leadership in advancing science for patients with chronic lymphocytic leukaemia.
“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.”
AMPLIFY is a randomised, global, multi-centre, open-label study. It is evaluating the efficacy and safety of Calquence in combination with venetoclax, with and without obinutuzumab, versus investigator’s choice of chemoimmunotherapy in previously untreated CLL adults.
The study excluded those with del(17p) or TP53 mutation.
Participants were randomly assigned in a 1:1:1 ratio to receive Calquence with venetoclax, Calquence with venetoclax and obinutuzumab, or standard-of-care chemoimmunotherapy.
The primary endpoint of the study is PFS, with additional secondary endpoints including OS, event-free survival, overall response rate, duration of response, and time to next treatment.
The trial was conducted across 27 countries in North and South America, Asia, Europe, and Oceania, enrolling patients from 2019 to 2021 during the COVID-19 pandemic.
Calquence, a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK), is designed to bind covalently to BTK, inhibiting its activity. This inhibition disrupts B-cell receptor signalling pathways crucial for B-cell proliferation and survival.
The drug is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the US, Japan, and many other countries, and for relapsed or refractory CLL and SLL in China. It is also approved for mantle cell lymphoma (MCL) in various countries, though not currently in Japan or the EU.
Calquence is undergoing extensive clinical evaluation for multiple B-cell malignancies, including CLL, MCL, and diffuse large B-cell lymphoma.
Venetoclax is an oral medication used to treat various types of blood cancers. It was developed by AbbVie in collaboration with Genentech, a member of the Roche Group.
