On September 4, 2023 AstraZeneca reported that Calquence (acalabrutinib), a next generation, selective Bruton’s tyrosine kinase (BTK) inhibitor, has been approved in China for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least one prior therapy (Press release, AstraZeneca, SEP 4, 2023, View Source [SID1234634856]).
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The approval by the National Medical Products Administration (NMPA) was based on positive results from two clinical trials, including the ASCEND Phase III trial of Calquence versus investigator’s choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) for patients with relapsed or refractory (R/R) CLL and an open-label, single-arm Phase I/II trial in China for patients with R/R CLL.1,2
CLL is the most prevalent type of adult leukaemia across the globe and represents approximately 6.4% of B-cell non-Hodgkin lymphoma patients in China.3
Professor Li Jianyong, Director of Haematology, People’s Hospital of Jiangsu Province, and Leader of China CLL Working Group, said: "Many people living with chronic lymphocytic leukaemia experience relapse and need additional treatment options to help manage their disease. I’m delighted that with this approval patients now have access to an established treatment that has already demonstrated effectiveness in many patients across the globe."
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Today’s approval is another step towards our goal of making Calquence available to as many patients as possible and offering physicians a treatment option with a well-established efficacy and tolerability profile. Patients with chronic lymphocytic leukaemia are often older and dealing with significant comorbidities, and tolerability is a critical factor in their treatment."
In the ASCEND Phase III trial, 88% of patients with R/R CLL treated with Calquence were alive and free from disease progression after 12 months compared with 68% of patients treated with IdR/BR.1 Longer-term follow-up data showed 62% of patients treated with Calquence were alive and had not progressed at 42 months versus 19% of patients treated with IdR/BR.
Additionally, results from a Phase I/II trial in Chinese adults with R/R CLL showed Calquence achieved an overall response rate (ORR) of 83.3%. At a median follow-up of 20.2 months, median progression-free survival (PFS) was not reached and the 12-month and 18-month PFS rates were 90.7% and 78.8%, respectively. The safety and tolerability of Calquence in these trials were consistent with that observed in previous clinical trials.1,2
Calquence is approved for the treatment of CLL and SLL in the US and Japan and is approved for the treatment of CLL in the EU and in several other countries worldwide in the treatment-naïve and R/R settings. Calquence is also approved in the US, China and several other countries for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU.
Notes
CLL
CLL is the most prevalent type of leukaemia in adults, with over 100,000 new cases globally in 2019.4 Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain.5 In CLL, there is an accumulation of abnormal lymphocytes within the bone marrow and in blood and lymph nodes. As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets. This could result in anaemia, infection and bleeding.6 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.
ASCEND
ASCEND (ACE-CL-309) is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy of Calquence in patients with relapsed or refractory CLL.1
In the trial, 310 patients were randomised (1:1) into two treatment arms.1 Patients in the first arm received Calquence monotherapy (100mg twice-daily until disease progression or unacceptable toxicity).1 Patients in the second arm received physician’s choice of either rituximab, a CD20 monoclonal antibody, in combination with idelalisib, a PI3-kinase inhibitor, or rituximab in combination with bendamustine, a chemotherapy.1
The primary endpoint at the interim analysis was PFS assessed by an independent review committee (IRC), and key secondary endpoints included investigator-assessed PFS, IRC and investigator-assessed ORR and duration of response, as well as overall survival (OS), patient-reported outcomes and time to next treatment.1
ASCEND is the first randomised Phase III trial to directly compare a BTK inhibitor as monotherapy to these combinations in relapsed or refractory CLL.1
Phase I/II trial in Chinese patients
The Phase I/II trial is an open-label, multicentre clinical trial evaluating pharmacokinetics, tolerability, safety and clinical efficacy of Calquence in adult Chinese patients with CLL who have received at least one prior therapy and other B-cell malignancies.2 In Phase I, patients with relapsed or refractory B-cell malignancies received a single dose of Calquence 100mg orally followed by a two-day washout period and subsequent treatment with Calquence 100mg orally twice daily in 28-day cycles, until progressive disease (PD) or treatment discontinuation (TD) for any other reason.2 In Phase II, patients with relapsed or refractory CLL (n=60) received Calquence 100mg orally twice daily until PD or TD for any other reason.2 The primary efficacy endpoint was ORR per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 classification assessed by Blinded Independent Central Review (BICR).2 Secondary endpoints were investigator-assessed ORR, BICR- and investigator-assessed time to response, duration of response and PFS, OS, safety including adverse events and Calquence plasma concentration.2
Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity.7 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.
Calquence has been used to treat 50,000 patients worldwide and is approved for the treatment of CLL and SLL in the US, approved for CLL in the EU and many other countries worldwide and approved in Japan for relapsed or refractory CLL and SLL.
As part of an extensive clinical development programme, AstraZeneca is currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being evaluated for the treatment of multiple B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenström’s macroglobulinaemia, marginal zone lymphoma and other haematologic malignancies.