AstraZeneca’s Calquence Gains U.S. Approval for First-Line Treatment of Mantle Cell Lymphoma, Following Positive Phase III Results

(IN BRIEF) AstraZeneca’s Calquence (acalabrutinib) has been approved by the U.S. FDA for the first-line treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation. The approval is based on positive results from the ECHO Phase III trial, showing significant improvement in progression-free survival (PFS) compared to standard chemoimmunotherapy. Calquence, now the first BTK inhibitor approved for this indication, offers a crucial new treatment option for MCL patients. The drug’s safety profile remained consistent with prior studies, and regulatory reviews are underway in other markets globally.

(PRESS RELEASE) CAMBRIDGE, 18-Jan-2025 — /EuropaWire/ — AstraZeneca has received approval from the U.S. Food and Drug Administration (FDA) for Calquence (acalabrutinib) in combination with bendamustine and rituximab to treat adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation. This approval follows the successful results of the ECHO Phase III trial, which demonstrated a significant progression-free survival (PFS) improvement of more than 16 months compared to traditional chemoimmunotherapy.

Calquence is now the first and only Bruton’s tyrosine kinase (BTK) inhibitor approved for first-line treatment of MCL in the U.S. The FDA granted this approval after Priority Review, based on data presented at the 2024 European Hematology Association Congress. MCL, a rare and aggressive form of non-Hodgkin lymphoma (NHL), is typically diagnosed in advanced stages, with over 21,000 new cases annually across key global markets.

Dr. Michael Wang, principal investigator of the ECHO trial, emphasized the significance of these results, stating, “The trial highlights the promise of acalabrutinib in setting a new standard of care for MCL, offering an effective, well-tolerated treatment for older patients dealing with this aggressive disease.”

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, further praised the approval, noting, “With Calquence’s demonstrated ability to extend progression-free survival by nearly 18 months, this approval provides a crucial new option for MCL patients in the U.S. and reinforces our belief in the role of Calquence across multiple blood cancers.”

Meghan Gutierrez, CEO of the Lymphoma Research Foundation, also welcomed the approval, stating, “Effective first-line treatments have been sorely needed for MCL, and this advancement offers patients a much-needed option to improve outcomes early in their treatment journey.”

Results from the ECHO trial showed that the combination of Calquence, bendamustine, and rituximab reduced the risk of disease progression or death by 27% compared to standard chemoimmunotherapy. The median PFS for patients on the Calquence combination was 66.4 months, compared to 49.6 months for those on chemoimmunotherapy alone.

Additionally, the approval converts Calquence’s previous accelerated approval for patients with relapsed or refractory MCL into full approval. The trial, which enrolled patients during the COVID-19 pandemic, showed even more promising results after censoring for COVID-related deaths, with a 36% reduction in the risk of disease progression or death in the Calquence-treated group.

The safety profile of Calquence remained consistent with previous studies, with no new safety signals identified. The FDA’s review process for this submission was conducted under Project Orbis, a collaboration among international regulatory authorities for the concurrent review of oncology medicines. Regulatory submissions are currently underway in other global markets, including the EU, Japan, Australia, Canada, and Switzerland.

Notes

Mantle cell lymphoma (MCL)
While MCL patients initially respond to treatment, patients do tend to relapse.4 MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; in the US, it is estimated that approximately 4,000 new patients are diagnosed with MCL each year.4,5

ECHO
ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to SoC chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=635) with previously untreated MCL.6 Patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, continuously, until disease progression or unacceptable toxicity. Additionally, all patients received six 28-day cycles of bendamustine on days 1 and 2 and rituximab on day 1 of each cycle, followed by rituximab maintenance for two years if patients achieved a response after induction therapy.6

The primary endpoint is PFS assessed by an Independent Review Committee; other efficacy endpoints include OS, overall response rate (ORR), duration of response (DoR) and time to response (TTR).6 The trial was conducted in 27 countries across North and South America, Europe, Asia and Oceania.6

The ECHO trial enrolled patients from May 2017 to March 2023, continuing through the COVID-19 pandemic. Prespecified PFS and OS analyses censoring for COVID-19 deaths were conducted to assess the impact of COVID-19 on the study outcome in alignment with the FDA. Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.6,7

Calquence
Calquence (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.8 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 more than 85,000 patients worldwide9 and is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US and Japan, approved for CLL in the EU and many other countries worldwide and approved in China for relapsed or refractory CLL and SLL. Calquence is also approved for the treatment of adult patients with previously untreated MCL in the US, and in 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.

As part of an extensive clinical development programme, Calquence is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma.

AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care in haematology. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases through innovative medicines and approaches that are shaped by insights from patients, caregivers and physicians.

In addition to our marketed products, we are spearheading the development of novel therapies designed to target underlying drivers of disease across multiple scientific platforms. Our acquisitions of Alexion, with expertise in rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., pioneers of autologous cell therapies, expand our haematology pipeline and enable us to reach more patients with high unmet needs through the end-to-end discovery, development and delivery of novel therapies.

AstraZeneca in oncology
AstraZeneca 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 Company’s 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.

AstraZeneca
AstraZeneca (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’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

References

Lymphoma Research Foundation. Mantle Cell Lymphoma. Available at: https://lymphoma.org/aboutlymphoma/nhl/mcl/. Accessed January 2025.
National Organization for Rare Disorders. Mantle Cell Lymphoma. Available at: https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/. Accessed January 2025.
AstraZeneca 2024. Q3 2024 Financial Results. Available at: https://www.astrazeneca.com/investor-relations.html. Accessed January 2025.
Cheah C, Seymour J, Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34(11):1256-1269. doi: 10.1200/JCO.2015.63.5904.
MD Anderson Cancer Center. What to know about mantle cell lymphoma. Available at: https://www.mdanderson.org/cancerwise/what-to-know-about-mantle-cell-lymphoma-symptoms-diagnosis-and-treatment.h00-159385101.html. Accessed January 2025.
ClinicalTrials.gov. A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL. Available at: https://clinicaltrials.gov/study/NCT02972840. Accessed January 2025.
Dube S, et al. Continued Increased Risk of COVID-19 Hospitalisation and Death in Immunocompromised Individuals Despite Receipt of ≥4 Vaccine Doses: Updated 2023 Results from INFORM, a Retrospective Health Database Study in England. Poster P0409 at ECCMID 2024.
Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).
Data on File, REF-236261. AstraZeneca Pharmaceuticals LP.

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AstraZeneca PLC

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