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AstraZenecas Calquence (acalabrutinib), a next generation, selective Brutons tyrosine kinase (BTK) inhibitor, has been conditionally approved in China for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This is the first approved indication for Calquence in China.

The conditional approval by the National Medical Products Administration (NMPA) was based on positive results from two clinical trials, including the ACE-LY-004 global Phase II trial in adults with relapsed or refractory MCL and a Phase I/ II trial in Chinese patients with relapsed or refractory MCL and other B-cell malignancies.1,2 Continued approval for this indication may be contingent upon verification of ongoing randomised controlled confirmatory trials.

MCL is typically an aggressive, rare form of non-Hodgkin lymphoma (NHL) that accounts for between 2-6% of all patients diagnosed with NHL in China. Patients are generally diagnosed around 60years of age, often at later stages of the disease.3

Jun Zhu, Chief Physician, Department of Lymphatic Oncology, Peking University Cancer Hospital, Beijing, said: Mantle cell lymphomaprogresses rapidly and responds poorly to conventional treatmentsuch as immunochemotherapy.Before the emergence of BTK inhibitors, there were few satisfactory treatment options forpatients.The next-generation BTK inhibitor Calquence has higher target selectivity, fewer side effects, and a higher response rate compared to currently available treatments. This approval of Calquence in China can provide a new treatment option which can better benefit patients with this disease.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: This approval for Calquence offers people living with mantle cell lymphoma in China an effective and tolerable new treatment option to help control their disease. As the first approval in China for Calquence, it is also an exciting step forward for AstraZeneca in blood cancers, enabling us to help more patients across the globe gain access to innovative treatments.

Results from the ACE-LY-004 Phase II trial showed at a median follow up of 15.2 months, investigator-assessed overall response rate (ORR) with Calquence was 80.6% (95% confidence interval [CI] 72.6-87.2), with a complete response (CR) achieved in 39.5% of patients with relapsed or refractory MCL (95% CI 30.9-48.7).1 Longer-term follow-up data showed at 38.1 months, patients treated with Calquence remained progression-free for a median of 22 months, with median overall survival (OS) of 59.2 months (95% CI 36.5-NE).4

Additionally, results from a Phase I/II trial conducted in China showed Calquence achieved a 82.4% ORR, with a CR achieved in 35.3% of patients with MCL based on a blinded independent central-review (BICR) analysis (95% CI 65.5-93.2). Calquence reduced the risk of disease progression or death by 51.5% (95% CI 33.3-67.0) at 12 months, with an estimated duration of response (DOR) of 65.5% (95% CI 66.6-93.3). The median DOR was not reached.2

The safety and tolerability of Calquence in these trials was consistent with that observed in previous clinical trials.1,2,4

Calquenceis approvedfor the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (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-nave and relapsed or refractory settings.Calquenceis also approved in the US and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy. Calquenceis not currently approved for the treatment of MCL in Japan or the EU.

Notes

Mantle cell lymphoma (MCL)MCL is a rare B-cell malignancy subtype and is typically clinically aggressive with a poor prognosis.3The epidemiology of MCL in Asia is not well documented, with few published datasets describing the incidence and outcomes.3MCL accounts for between 2-6% of all patients diagnosed with NHL China.3Patients are generally diagnosed around 60years of age and often at later stages of disease (Stage III or IV).3

ACE-LY-004ACE-LY-004 is an open-label, single-arm Phase II clinical trial evaluating Calquence in adult patients with relapsed or refractory MCL.5 Patients in the trial were adults with MCL and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or lower who had relapsed or were refractory to 1-5 prior therapies, had no prior BTK/BCL-2 inhibitor exposure, and did not require warfarin/vitamin K antagonists. Patients received oral Calquence 100mg twice-daily until progressive disease or toxicity. ORR (investigator-assessed partial response or better per Lugano classification), DOR, progression-free survival (PFS), OS and safety were assessed.1

Phase I/II trial in Chinese patientsThe Phase I/II trial is an open-label, multicentre clinical trial evaluatingpharmacokinetics, safety and efficacy ofCalquencein adult Chinese patients with relapsed or refractory MCL and other advanced B-cell malignancies.2In Phase I, patients with relapsed or refractory B-cell malignancies received a single dose ofCalquence100mg orally followed by a two-day washout period and subsequent treatment withCalquence100mg orally twice daily in 28-day cycles, until progressive disease (PD) or treatment discontinuation (TD) for any other reason. In Phase II, patients with relapsed or refractory MCL and ECOG status of 2 or lower receivedCalquence100mg orally twice daily in 28-day cycles until PD or TD. The primary efficacy endpoint was ORR per Lugano classification for NHL assessed by BICR. Secondary endpoints were investigator-assessed ORR, BICR- and investigator-assessed time to response, DOR, PFS, OS and adverse events.2

CalquenceCalquence(acalabrutinib) is a next-generation, selective inhibitor of BTK.Calquencebinds covalently to BTK, thereby inhibiting its activity.6In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquenceis 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 Calquencein 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, Waldenstrms macroglobulinaemia, marginal zone lymphoma and other haematologic malignancies.

AstraZeneca in haematologyAstraZeneca is pushing the boundaries of science to redefine care in haematology. We have expanded our commitment to patients with haematologic conditions, not only in oncology but also in rare diseases with the acquisition of Alexion, allowing us to reach more patients with high unmet needs. By applying our deep understanding of blood cancers, leveraging our strength in solid tumour oncology and delivering on Alexions pioneering legacy in complement science to provide innovative medicines for rare diseases, we are pursuing the end-to-end development of novel therapies designed to target underlying drivers of disease.

By targeting haematologic conditions with high unmet medical needs, we aim to deliver innovative medicines and approaches to improve patient outcomes. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases, shaped by insights from patients, caregivers and physicians to have the most meaningful impact.

AstraZeneca in oncologyAstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Companys focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZenecaAstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visitastrazeneca.comand follow the Company on Twitter@AstraZeneca.

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