Positive results from the Phase III ASCEND trial of acalabrutinib in previously-treated patients with chronic lymphocytic leukaemia (CLL) have been revealed.
Results showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) with acalabrutinib monotherapy compared to a combination regimen of rituximab plus physician’s choice of idelalisib or bendamustine.
Importantly, the safety and tolerability of acalabrutinib was consistent with the known profile.
José Baselga, Executive Vice President, R&D Oncology said: “Acalabrutinib is the first BTK inhibitor to show benefit in a phase III trial as a monotherapy compared to current standard-of-care combinations used in relapsed or refractory chronic lymphocytic leukaemia. We look forward to presenting detailed results at a forthcoming medical meeting.”
ASCEND is the first of two Phase III CLL trials expected to read out in 2019.
The second is ELEVATE-TN (ACE-CL-007) in treatment-naïve, front-line CLL.
Acalabrutinib is currently approved for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) in the US, Brazil, the UAE, and Qatar, and is being developed for the treatment of CLL and other blood cancers.
ASCEND (ACE-CL-309) is a global, randomised, multi-centre, open-label phase III trial evaluating the efficacy of acalabrutinib in previously-treated patients with CLL.
In the trial, 310 patients were randomised (1:1) into two groups.
Patients in the first group received acalabrutinib monotherapy (100mg twice daily until disease progression).
Patients in the second group received rituximab plus physician’s choice of idelalisib or bendamustine.
The primary endpoint is PFS assessed by an independent review committee (IRC) and key secondary endpoints include physician-assessed PFS, IRC and physician-assessed overall response rate and duration of response, as well as overall survival, patient reported outcomes and time to next treatment (TTNT).
Acalabrutinib was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Acalabrutinib is an inhibitor of Bruton tyrosine kinase (BTK).
Acalabrutinib binds covalently to BTK, thereby inhibiting its activity.
In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.
Acalabrutinib is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenstrom macroglobulinaemia, follicular lymphoma, and multiple myeloma and other haematologic malignancies.
Several Phase III clinical trials in CLL are ongoing, including ASCEND, ELEVATE-TN, ELEVATE-RR (ACE-CL-006) which are evaluating the effect of acalabrutinib versus. ibrutinib in previously-treated CLL.
Furthermore, ACE-CL-311 is evaluating acalabrutinib in combination with venetoclax and obinutuzumab in previously-untreated fit patients with CLL.
About chronic lymphocytic leukaemia (CLL)
CLL is the most common type of leukaemia in adults.
In the US, it accounts for approximately one in four new cases of leukaemia, with the average age at the time of diagnosis being approximately 70 years of age.
In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.
As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.
This could result in anaemia, infection and bleeding.
B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.
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