AstraZeneca Plc - Calquence Phase III ELEVATE-TN trial met primary
Calquence Phase III ELEVATE-TN trial met primary endpoint at interim analysis in previously-untreated chronic lymphocytic leukaemia
Calquence alone or in combination significantly increased the time patients lived without disease progression
AstraZeneca today announced positive results from the Phase III ELEVATE-TN trial of Calquence (acalabrutinib) in patients with previously-untreated chronic lymphocytic leukaemia (CLL), the most common type of leukaemia in adults.1 This is the second Calquence pivotal trial in CLL to meet its primary endpoint early, following the positive results of the ASCEND trial, announced in May.
The trial met its primary endpoint; Calquence in combination with obinutuzumab demonstrated a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) when compared with the chemotherapy-based combination of chlorambucil and obinutuzumab.
The trial also met a key secondary endpoint showing Calquence monotherapy achieved a statistically-significant and clinically-meaningful improvement in PFS compared to the chemotherapy and obinutuzumab regimen.
The safety and tolerability of Calquence was consistent with its established profile.
José Baselga, Executive Vice President, Oncology R&D said: "These findings confirm the superiority of Calquence as a monotherapy and also in combination over standard-of-care treatments for chronic lymphocytic leukaemia. The positive results from both the ELEVATE-TN and ASCEND trials will serve as the foundation for regulatory submissions later this year."
AstraZeneca plans to present detailed results from ELEVATE-TN at a forthcoming medical meeting. Additionally, AstraZeneca will present full results from the Phase III ASCEND clinical trial in relapsed or refractory CLL as a late-breaking abstract at the upcoming European Hematology Association (EHA) Annual Congress on 16 June 2019 (Abstract #LB2606).
Calquence is currently approved for the treatment of adults with relapsed or refractorymantle cell lymphoma (MCL) in the US, Brazil, the UAE, and Qatar and is being developed for the treatment of CLL and other blood cancers.
ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of Calquence alone or in combination with obinutuzumab vs. chlorambucil in combination with obinutuzumab in previously-untreated patients with CLL. In the trial, 535 patients were randomised (1:1:1) into three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab. Patients in the second arm received Calquence (100mg twice daily until disease progression) in combination with obinutuzumab. Patients in the third arm received Calquencemonotherapy (100mg twice daily until disease progression).2
The primary endpoint is PFS in the Calquence and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee (IRC), and a key secondary endpoint is IRC-assessed PFS in the Calquencemonotherapy arm compared to the chlorambucil and obinutuzumab arm. Other secondary endpoints include objective response rate, time to next treatment and overall survival.2
Calquence (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.
Calquence is an inhibitor of Bruton tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.3 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.
As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in 26 company-sponsored clinical trials. Calquence 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) evaluating acalabrutinib vs. ibrutinib in patients with previously-treated high-risk CLL, and ACE-CL-311 evaluating acalabrutinib in combination with venetoclax and with/without obinutuzumab in patients with previously-untreated CLL without 17p deletion or TP53 mutation.
About chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in adults, with an estimated 191,000 new cases globally and 20,720 new cases in the US annually, and prevalence that is expected to grow with improved treatment.1,4,5,6 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.1 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.1 This could result in anaemia, infection and bleeding.1 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.
About AstraZeneca in haematology
Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company's haematology franchise includes two US FDA-approved medicines and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca's haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.
In October 2018, AstraZeneca and Innate Pharma announced a global strategic collaboration that included Innate Pharma licensing the US commercial rights of Lumoxiti (moxetumomab pasudotox-tdfk), and with support from AstraZeneca, will continue EU development and commercialisation, pending regulatory submission and approval.