# Acalabrutinib

Source: https://onco.cc/drugs/acalabrutinib/  
OnCo record `acalabrutinib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Acalabrutinib is a cleaner BTK blocker with fewer heart and bleeding problems than ibrutinib. In February 2026 it became half of the first all-oral, fixed-duration CLL regimen.

## Summary

ELEVATE-TN (frontline, 6-year median PFS not reached vs 27.8 months for chlorambucil-obinutuzumab; OS benefit for acalabrutinib-obinutuzumab), ELEVATE-RR (non-inferior PFS to ibrutinib with less atrial fibrillation), and AMPLIFY (acalabrutinib + venetoclax ± obinutuzumab, fixed duration: 3-year PFS 76.5%/83.1% vs 66.5% for chemoimmunotherapy) led to the 19 February 2026 approval of acalabrutinib-venetoclax for previously untreated CLL without del(17p)/TP53. Also approved in MCL (first-line 2025, ECHO). Tablet formulation removed the acid-suppressant interaction.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Brand: Calquence
- Modality: Small-molecule covalent BTK inhibitor (second generation)
- Mechanism: Highly selective covalent BTK inhibitor (C481) with minimal EGFR/TEC/ITK activity.
- Approvals: US 2017: Relapsed MCL (accelerated); US 2019: CLL/SLL, first-line and relapsed (ELEVATE-TN, ASCEND); US 2026: Fixed-duration acalabrutinib + venetoclax, previously untreated CLL/SLL without del(17p)/TP53 (AMPLIFY)
- Dosing: Oral; 100 mg twice daily continuously (monotherapy), or 100 mg twice daily for 14 cycles with venetoclax added from cycle 3 (AMPLIFY fixed-duration)
- Toxicity (grade 3+): Neutropenia 23%

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Acalabrutinib
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Acalabrutinib

## Connected records

- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Chronic lymphocytic leukaemia, first treatment](https://onco.cc/cancers/cll-treatment-naive/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Relapsed or refractory chronic lymphocytic leukaemia](https://onco.cc/cancers/cll-relapsed/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/), [Waldenström macroglobulinaemia](https://onco.cc/cancers/waldenstrom/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [ITK](https://onco.cc/targets/itk/), [TEC](https://onco.cc/targets/tec/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/)
- trials: [A Combination of Acalabrutinib With R-CHOP in Subjects With Previously Untreated Non-GCB DLBCL (ACE-LY-312)](https://onco.cc/trials/nct04529772/), [A Study of Acalabrutinib Plus Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma](https://onco.cc/trials/nct05951959/), [A Study of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma](https://onco.cc/trials/nct05057494/), [A Study of Acalabrutinib vs Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in R/R CLL](https://onco.cc/trials/nct02970318/), [A Study of ACP-196 (Acalabrutinib) in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy](https://onco.cc/trials/nct02717611/), [A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL](https://onco.cc/trials/nct02972840/), [A Study to Evaluate Acalabrutinib, in Combination With the R-CHOP Standard of Care, for Previously Untreated Mantle Cell Lymphoma in Spain](https://onco.cc/trials/nct07029737/), [A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL)](https://onco.cc/trials/nct06428019/), [A Study to Investigate Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Acalabrutinib in Adults With Previously Untreated Chronic Lymphocytic Leukemia](https://onco.cc/trials/nct07277231/), [Acalabrutinib, Umbralisib, and Ublituximab (AU2) In Relapsed and Untreated CLL](https://onco.cc/trials/nct04624633/), [ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia](https://onco.cc/trials/nct02029443/), [AMPLIFY](https://onco.cc/trials/amplify/), [An Open-label, Phase 2 Study of ACP-196 (Acalabrutinib) in Subjects With Mantle Cell Lymphoma](https://onco.cc/trials/nct02213926/), [An Open-label, Phase 2 Study of ACP-196 in Subjects With Waldenström Macroglobulinemia](https://onco.cc/trials/nct02180724/), [ARCHED](https://onco.cc/trials/arched/), [BELLWAVE-011](https://onco.cc/trials/bellwave-011/), [ELEVATE-TN](https://onco.cc/trials/elevate-tn/), [Phase 2 Study of Disease Risk Mutation-Guided Finite Acalabrutinib+Venetoclax for Relapsed CLL Post-1L Finite cBTKi+BCL2i ± Obinutuzumab](https://onco.cc/trials/nct07024706/), [Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL](https://onco.cc/trials/nct04502394/), [Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)](https://onco.cc/trials/nct02477696/), [Study of Acalabrutinib Alone or in Combination Therapy in Subjects With B-cell Non-Hodgkin Lymphoma](https://onco.cc/trials/nct02180711/), [Study of Acalabrutinib and Rituximab in Untreated Elderly and/or Frail Patients With DLBCL](https://onco.cc/trials/nct05952024/), [Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malign](https://onco.cc/trials/nct03932331/), [Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia](https://onco.cc/trials/nct04075292/), [Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)](https://onco.cc/trials/nct04662255/)
- pairings: [BTK inhibitor + venetoclax, fixed duration](https://onco.cc/pairings/btki-plus-venetoclax-fixed-duration/), [Caution: ibrutinib in patients with cardiac risk](https://onco.cc/pairings/btki-ibrutinib-cardiac-caution/)
- ideas: [BTK degraders to pre-empt resistance in frontline CLL](https://onco.cc/ideas/idea-btk-degrader-frontline/), [Fixed-duration, chemotherapy-free first-line treatment for the indolent lymphomas](https://onco.cc/ideas/lymphoma-ev-fixed-duration-chemotherapy-free-first-line/)
- terms: [BTK C481S, PLCG2 and BCL2 G101V resistance mutations](https://onco.cc/terms/btki-bcl2i-resistance-mutations/), [CLL-IPI (chronic lymphocytic leukaemia prognostic index)](https://onco.cc/terms/cll-ipi/), [MIPI (Mantle Cell Lymphoma International Prognostic Index)](https://onco.cc/terms/mipi/), [MYD88 L265P and CXCR4 mutations](https://onco.cc/terms/myd88-l265p/), [What the NHS in England funds for lymphoma, appraisal by appraisal](https://onco.cc/terms/lymphoma-tx-uk-access/)
- biomarkers: [BTK resistance mutations: C481S, and L528W and T474I after the non-covalent inhibitors](https://onco.cc/biomarkers/btk-c481s/)
- key papers: [Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma](https://onco.cc/key-papers/paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025/), [AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients](https://onco.cc/key-papers/paper-amplify-acalabrutinib-venetoclax-nejm-2025/), [ELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLL](https://onco.cc/key-papers/paper-elevate-tn-acalabrutinib-lancet-2020/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)
- institutions: [The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute](https://onco.cc/institutions/osu-james/)

---
JSON: https://onco.cc/api/v1/entities/acalabrutinib.json