FDA Approves Venclexta Plus Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia
The FDA has approved the combination of Venclexta (venetoclax) plus acalabrutinib as the first all-oral, fixed-duration regimen for previously untreated adults with chronic lymphocytic leukemia, based on Phase III AMPLIFY study results.
The U.S. Food and Drug Administration has approved the combination regimen of Venclexta (venetoclax) plus acalabrutinib for the treatment of previously untreated adults with chronic lymphocytic leukemia (CLL), based on results from the Phase III AMPLIFY study. The approval marks the first and only all-oral, fixed-duration regimen for this indication.
The approval was based on results from the Phase III AMPLIFY study, which demonstrated that Venclexta plus acalabrutinib was superior to chemoimmunotherapy. Study results showed the combination regimen reduced the risk of disease progression or death by 35% versus chemoimmunotherapy (HR 0.65; 95% CI: 0.49-0.87; p=0.0038). At a median follow-up of 42.6 months, median progression-free survival was not reached for the combination regimen (95% CI: 51.1 months, not reached) versus 47.6 months (95% CI: 43.3 months, not reached) for chemoimmunotherapy.
The combination regimen is administered for a fixed-duration of 14 cycles, each consisting of 28 days. Results from the AMPLIFY trial were presented at the American Society of Hematology 2024 Annual Meeting and published in The New England Journal of Medicine.
The safety profile of Venclexta plus acalabrutinib is consistent with the known safety profile of each individual therapy alone. In chronic lymphocytic leukemia or small lymphocytic lymphoma, the most common adverse reactions (≥20%) for Venclexta when given in combination with acalabrutinib were neutropenia, headache, diarrhea, musculoskeletal pain, and COVID-19. The most common serious adverse reactions (≥2%) in patients receiving Venclexta plus acalabrutinib were COVID-19, including COVID-19 pneumonia (9%), second primary malignancies (2.7%), and neutropenia (2.1%).
The approval expands Genentech's fixed-duration portfolio by providing eligible first-line patients another option alongside the established Venclexta plus Gazyva regimen. Venclexta is already approved for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and in combination regimens for newly diagnosed AML patients aged 75 or older, or those ineligible for standard chemotherapy.
The AMPLIFY study (NCT05197192) is an AstraZeneca-sponsored global, multi-center, open-label, Phase III study evaluating fixed-duration Venclexta (venetoclax) plus acalabrutinib, alone or combined with Gazyva (obinutuzumab), compared to investigator's choice of chemoimmunotherapy in patients with previously untreated chronic lymphocytic leukemia (CLL) without 17p deletion or TP53 mutation. In AMPLIFY, patients were randomized 1:1:1 to receive either Venclexta plus acalabrutinib, Venclexta plus acalabrutinib with Gazyva for a fixed duration, or chemoimmunotherapy.
Chronic lymphocytic leukemia (CLL) is a slow-growing cancer in the blood and bone marrow. It is the most common type of leukemia in the U.S., with an estimated number of 22,760 new cases of CLL in 2026. Although signs of CLL may disappear for a while after initial treatment, many people require additional treatment due to the return of cancerous cells.
Venclexta is a first-in-class targeted medicine designed to bind selectively and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta is developed by AbbVie and Genentech, and is jointly commercialized in the United States and marketed by AbbVie outside the U.S.