Fixed-duration CALQUENCE® plus venetoclax improves progression-free survival in 1st-line CLL: AMPLIFY Phase III trial

Positive high-level results from an interim analysis of the AMPLIFY Phase III trial revealed that a fixed duration of AstraZeneca’s CALQUENCE® (acalabrutinib) combined with venetoclax, with or without obinutuzumab, significantly improved progression-free survival (PFS) in previously untreated adult patients with chronic lymphocytic leukemia (CLL) compared to standard chemoimmunotherapy. Furthermore, there was a favorable trend in overall survival (OS) for the CALQUENCE combination, although OS data were immature at the time, and the trial will continue to evaluate this endpoint.

Chronic lymphocytic leukemia is characterized by the abnormal production of white blood cells, making it the most common type of leukemia in adults worldwide. Despite being considered incurable, many patients live for several years with the disease, often requiring continuous treatment. An estimated 40,000 patients receive first-line standard care treatment.

Dr. Jennifer R. Brown, the principal investigator of the trial, emphasized the significance of these findings. She noted that the AMPLIFY results highlight the potential of acalabrutinib and venetoclax, with or without obinutuzumab, as effective and well-tolerated fixed-duration treatments for CLL. This is crucial as it allows patients to take breaks from treatment, potentially reducing long-term adverse effects and drug resistance, thereby improving quality of life.

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, stated that the PFS and OS results from the trial underscore the potential benefits of including a Bruton tyrosine kinase (BTK) inhibitor in a fixed-duration regimen, fortifying AstraZeneca's commitment to advancing CLL treatment. If approved, CALQUENCE would be the only second-generation BTK inhibitor available for both treat-to-progression and fixed-duration therapy, offering more options for patients and healthcare providers.

The safety and tolerability of the treatment were consistent with the known profiles of the individual medications, with no new safety concerns identified and low rates of cardiac toxicity. The data from the trial will be presented at an upcoming medical meeting and shared with global regulatory authorities.

CALQUENCE is a BTK inhibitor indicated for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Its approval was based on the overall response rate, with continued approval possibly dependent on the results of confirmatory trials. CALQUENCE is also approved for treating adult patients with CLL or small lymphocytic lymphoma (SLL).

Serious adverse effects reported in patients treated with CALQUENCE include infections, hemorrhage, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity. The most common adverse reactions in patients with relapsed or refractory MCL include anemia, thrombocytopenia, headache, neutropenia, diarrhea, fatigue, myalgia, and bruising, with major non-hematological adverse reactions being diarrhea.

For patients with previously untreated CLL, serious adverse reactions were reported in a significant percentage of patients, primarily due to pneumonia. Dose reductions or discontinuations due to adverse reactions were relatively low. For patients receiving CALQUENCE for relapsed/refractory CLL, serious adverse reactions included lower respiratory tract infections, with fatal adverse reactions occurring in a small percentage of patients.

CALQUENCE's efficacy and safety were evaluated in the AMPLIFY trial, a global, multi-center, phase III trial comparing CALQUENCE in combination with venetoclax, with or without obinutuzumab, to standard chemoimmunotherapy in patients with previously untreated CLL. The primary endpoint was PFS, with secondary endpoints including OS, event-free survival, overall response rate, duration of response, and time to next treatment.

CALQUENCE has been used to treat over 80,000 patients globally and is approved for CLL and SLL in various countries. It is also approved for MCL treatment in multiple countries, excluding Japan and the EU for MCL. CALQUENCE is currently being evaluated in various clinical trials for different B-cell blood cancers, including CLL, MCL, and diffuse large B-cell lymphoma.