Calquence (acalabrutinib) is a small-molecule Bruton’s tyrosine kinase inhibitor being developed by AstraZeneca. The U.S Food and Drug Administration (FDA) recently granted Calquence accelerated approval to treat adults with mantle cell lymphoma (MCL) who have received at least one prior therapy.

How Calquence works

MCL is a rare type of non-Hodgkin’s lymphoma that originates in immune cells (called B-cells) from the “mantle zone” of the lymph nodes. B-cells are responsible for combating infections or threats against the body by producing antibodies.

Patients with MCL have a short remission duration to standard therapies and a median overall survival of 4-5 years.

Calquence is a highly selective and potent cell signal inhibitor that works by blocking the activity of a specific protein called Bruton’s tyrosine kinase, or BTK. BTK is a part of a pathway that helps B-cells to stay alive and divide. By forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells, Calquence helps kill and reduce the number of cancer B-cells. This stops or slows the progression of lymphoma.

Calquence in clinical trials

The FDA based its approval of Calquence on findings from the Phase 2 ACE-LY-004 clinical trial (NCT02213926) designed to evaluate the effectiveness and safety of the treatment in 124 patients with relapsed (returning) or refractory (drug-resistant) MCL. Patients who were treated with a prior BTK inhibitor were excluded from the trial. The trial measured the number of patients who experienced complete or partial shrinkage of their tumors after treatment (overall response rate). The results showed that 40 percent of patients had a complete response and 41 percent experienced a partial response. The median duration of response was not yet reached at the time of analysis, with responses ongoing at more than 20 months.

AstraZeneca is now conducting a Phase 3 clinical trial (NCT02972840) called ACE-LY-308 to evaluate Calquence in combination with bendamustine and Rituxan as a potential first-line treatment for patients with MCL. The trial is currently recruiting patients in the U.S., Australia, Europe, Canada, Hong Kong, Israel, Korea, New Zealand, Russia, and Ukraine.

Apart from MCL, Calquence also is being developed for the treatment of other blood cancers including follicular lymphoma, chronic lymphocytic leukemia (CLL), Waldenström macroglobulinemia (WM), diffuse large B-cell lymphoma, and multiple myeloma.

It also is being studied as a monotherapy and combination therapy for solid tumors. So far, 29 clinical trials across the world with more than 2,500 patients have been completed or are underway.

Other details

The most common side effects caused by Calquence include nausea, diarrhea, fatigue and muscle pain (myalgia), lower urinary tract infections, and treatment-related loss of white blood cells and platelets (anemia). Serious side effects include bleeding and irregular heartbeat. Women who are breastfeeding should not take Calquence because it may cause harm to a newborn baby.

Calquence also was granted orphan drug designation by the FDA for the treatment of patients with MCL and by the European Commission for the treatment of patients with CLL, MCL, and WM.

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