Acalabrutinib

Acalabrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK). Acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity.

• CALQUENCE is a kinase inhibitor indicated: • In combination with bendamustine and rituximab for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT). (1.1 ) • For the treatment of adult patients with MCL who have received at least one prior therapy.ICD-10: C85.90

• None. None.contraindicated

• Recommended dose is 100 mg orally approximately every 12 hours; swallow whole with water and with or without food. ( 2.1 ) • Advise patients not to chew, crush, dissolve, or cut tablets. ( 2.1 ) • Manage toxicities using treatment interruption, dose reduction, or discontinuation. ( 2.3 ) • Avoid CALQUENCE in patients with severe hepatic impairment. ( 8.6 ) 2.1 Recommended Dosage CALQUENCE Administration Instructions Advise patients to swallow tablet whole with water. Advise patients not to chew, crush, dissolve, or cut the tablets. CALQUENCE may be taken with or without food. If a dose of CALQUENCE is missed by more than 3 hours, it should be skipped, and the next dose should be taken at its regularly scheduled time. Extra tablets of CALQUENCE should not be taken to make up for a missed dose. CALQUENCE as Monotherapy For patients with MCL, CLL or SLL, the recommended dosage of CALQUENCE is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity. CALQUENCE in Combination with Bendamustine and Rituximab For patients with previously untreated MCL, the recommended dosage of CALQUENCE is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity. Start CALQUENCE on Day 1 of Cycle 1 (each cycle is 28 days) and administer until disease progression or unacceptable toxicity. Administer bendamustine 90 mg/m 2 on Days 1 and 2 and rituximab 375 mg/m 2 on Day 1 of Cycle 1 and continue for a total of 6 cycles.

• Serious and Opportunistic Infections: Monitor for signs and symptoms of infection and treat promptly. ( 5.1 ) • Hemorrhage: Monitor for bleeding and manage appropriately. ( 5.2 ) • Cytopenias: Monitor complete blood counts regularly. ( 5.3 ) • Second Primary Malignancies: Other malignancies have occurred, including skin cancers and other solid tumors. Advise patients to use sun protection. ( 5.4 ) • Cardiac Arrhythmias: Monitor for symptoms of arrhythmias and manage. ( 5.5 ) • Hepatotoxicity, Including Drug Induced Liver Injury: Monitor hepatic function throughout treatment. ( 5.6 ) 5.1 Serious and Opportunistic Infections Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE. Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 29% of 2,055 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (18% of all patients, including pneumonia in 14%) [see Adverse Reactions (6.1) ] . These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 8% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: • Serious and Opportunistic Infections [see Warnings and Precautions (5.1) ] • Hemorrhage [see Warnings and Precautions (5.2) ] • Cytopenias [see Warnings and Precautions (5.3) ] • Second Primary Malignancies [see Warnings and Precautions (5.4) ] • Cardiac Arrhythmias [see Warnings and Precautions (5.5) ] • Hepatotoxicity, including DILI [see Warnings and Precautions (5.6) ] The most common adverse reactions (≥ 30%), excluding laboratory abnormalities, are upper respiratory tract infection, diarrhea, headache, and musculoskeletal pain. The most common Grade 3 or 4 laboratory abnormalities (≥ 10%) are absolute neutrophil count decreased, uric acid increased, absolute lymphocyte count decreased, and platelets decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the Warnings and Precautions reflect exposure to CALQUENCE 100 mg approximately every 12 hours in 2,055 patients with hematologic malignancies. Treatment includes CALQUENCE monotherapy in 1258 patients in 9 trials, and CALQUENCE combinations in 797 patients in 4 trials.

• Pregnancy: May cause fetal harm and dystocia. ( 8.1 ) • Lactation: Advise not to breastfeed. ( 8.2 ) • Severe Hepatic Impairment: Avoid use of CALQUENCE. ( 8.6 ) 8.1 Pregnancy Risk Summary Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of acalabrutinib to animals during organogenesis resulted in dystocia in rats and reduced fetal growth in rabbits at maternal exposures (AUC) 2 times exposures in patients at the recommended dose of 100 mg approximately every 12 hours ( see Data ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In a combined fertility and embryo-fetal development study in female rats, acalabrutinib was administered orally at doses up to 200 mg/kg/day starting 14 days prior to mating through gestational day [GD] 17.

Metabolism

Acalabrutinib and its active metabolite, ACP-5862, exposures increase proportionally with dose across a dose range of 75 to 250 mg (0.75 to 2.5 times the approved recommended single dosage) in patients with B-cell malignancies. At the recommended dose of 100 mg twice daily, the geometric mean (% coefficient of variation [CV]) daily area under the plasma drug concentration over time curve (AUC 24h ) and maximum plasma concentration (C max ) for acalabrutinib were 1843 (38%) ng•h/mL and 563 (29%) ng/mL, respectively, and for ACP-5862 were 3947 (43%) ng•h/mL and 451 (52%) ng/mL, respectively.

• Oct 31, 2017NDANDA210259Astrazeneca
• Aug 3, 2022NDANDA216387Astrazeneca

1. 1Death2,01818%
2. 2Fatigue6475.7%
3. 3Headache6045.3%
4. 4Product Dose Omission Issue4293.7%
5. 5Diarrhoea3933.4%
6. 6Fall3393.0%
7. 7Dyspnoea3152.8%
8. 8Contusion3082.7%
9. 9Malignant Neoplasm Progression3062.7%
10. 10Pneumonia3002.6%
11. 11Asthenia2922.6%
12. 12Pain2702.4%
13. 13Atrial Fibrillation2692.4%
14. 14Off Label Use2612.3%
15. 15Nausea2482.2%

The 10 most recently updated of 187 ClinicalTrials.gov registrations naming Acalabrutinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Nemtabrutinib (MK-1026) Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in First Line (1L) Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) (MK-1026-011/BELLWAVE-011)
  Recruiting · Phase 3 · Interventional · 1,200 enrolled · Merck Sharp & Dohme LLC
  NCT06136559updated 2026-06-12
• Acalabrutinib With R-CHOP in Previously Untreated Mantle Cell Lymphoma
  Active not recruiting · Phase 2 · Interventional · 105 enrolled · University Health Network, Toronto
  NCT04566887updated 2026-06-12
• A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 190 enrolled · ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
  NCT03162536updated 2026-06-12
• Acalabrutinib and Obinutuzumab for the Treatment of Chronic Lymphocytic Leukemia
  Active not recruiting · Phase 2 · Interventional · 60 enrolled · M.D. Anderson Cancer Center
  NCT04505254updated 2026-06-12
• A Study to Evaluate Acalabrutinib, in Combination With the R-CHOP Standard of Care, for Previously Untreated Mantle Cell Lymphoma in Spain
  Recruiting · Phase 2 · Interventional · 55 enrolled · AstraZeneca
  NCT07029737updated 2026-06-11
• A Pilot Study of Acalabrutinib in Relapsed/Refractory Primary and Secondary CNS Lymphomas
  Active not recruiting · Phase 2 · Interventional · 10 enrolled · UNC Lineberger Comprehensive Cancer Center
  NCT04548648updated 2026-06-10
• A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies
  Recruiting · Phase 1 · Phase 2 · Interventional · 408 enrolled · AstraZeneca
  NCT06564038updated 2026-06-10
• Acalabrutinib Maleate and Bortezomib for Patients With HLA Antibodies
  Not yet recruiting · Phase 3 · Interventional · 42 enrolled · The First Affiliated Hospital of Soochow University
  NCT07635511updated 2026-06-09
• A Study on Limiting Treatment Time With Acalabrutinib Combined With Obinutuzumab in People With CLL or SLL
  Active not recruiting · Phase 2 · Interventional · 55 enrolled · Memorial Sloan Kettering Cancer Center
  NCT04722172updated 2026-06-04
• A Study to Investigate Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Acalabrutinib in Adults With Previously Untreated Chronic Lymphocytic Leukemia
  Recruiting · Phase 3 · Interventional · 500 enrolled · BeOne Medicines
  NCT07277231updated 2026-06-03

Frequently asked questions

How does Acalabrutinib work?

Acalabrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK). Acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity.

What is Acalabrutinib used for?

According to FDA labeling, Acalabrutinib carries indications including: CALQUENCE is a kinase inhibitor indicated: • In combination with bendamustine and rituximab for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT). (1.1 ) • For the treatment of adult patients with MCL who have received at least one prior therapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Acalabrutinib?

Acalabrutinib is classified as Bruton's tyrosine kinase (BTK) inhibitors, Kinase Inhibitor, Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Acalabrutinib?

Acalabrutinib is marketed under brand names including Calquence.

What are the contraindications for Acalabrutinib?

Acalabrutinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.