Calquence (acalabrutinib) / AstraZeneca - LARVOL DELTA

Clinical Profile for CALQUENCE*(acalabrutinib) (SOHO 2025) - "This activity is sponsored by AstraZeneca"

Clinical • Oncology

A Pilot "Window-3" Study of Acalabrutinib Plus Rituximab Followed by Brexucabtagene Autoleucel Therapy in Patients With Previously Untreated High-risk Mantle Cell Lymphoma (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • BIRC3 • CCND1 • CD20 • FAT1 • KMT2D • NOTCH2 • NSD2 • POT1 • TP53 • UBR5

Calquence: “Extension of indication to include CALQUENCE in combination with venetoclax with or without obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL), based on interim results from study AMPLIFY (D8221C00001)…as a consequence, sections 4.1, 4.2, 4.4, 4.8, and 5.1 of the SmPC are updated.” (European Medicines Agency) - CHMP Final Minutes of the meeting on 22 - 25 Apr 2025: “The committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable”

CHMP • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology

Triplet Therapies in Chronic Lymphocytic Leukemia. (PubMed, Hematol Oncol Clin North Am) - "Triplet therapy regimens, which we define as the combination of a BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib, or pirtobrutinib), BCL2 inhibitor (venetoclax or sonrotoclax), and a CD20 antibody (obinutuzumab), have been developed in chronic lymphocytic leukemia (CLL). Herein, we comprehensively review the available clinical data for triplet regimens in treatment-naïve CLL, including an evidence-based discussion of the role of TP53 aberrancy in patients receiving triplet therapies, and of retreatment options after frontline triplet therapy. We also review ongoing trials with potential to further define the role of triplet therapies in treatment-naïve CLL."

Journal • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • TP53

Therapy Sequencing in Relapsed/Refractory MCL (ICML 2025) - P1, P1/2, P2, P3 | "Although a direct comparison between them has only been performed for ibrutinib and temsirolimus [23], covalent BTK inhibitor (cBTKi) single agent therapy has been consolidated as the standard of care after first-line CIT. Moreover, to address cBTKi failure, two anti-CD19 CAR-T cell therapy products, brexucabtagene autoleucel [20, 21] and lisocabtagene maraleucel [22], and the first noncovalent BTKi, pirtobrutinib [19], have recently been approved...Liso-cel only FDA approved; CIT, chemoimmunotherapy options include BR, R-BAC, R-CHOP, R-DHAP or R-DHAOx, R-GEMOx, paliative options (avoid bendamustine pre-CART apheresis); pirtobrutinib, available after cBTKi failure in second-line (EMA) but third-line (FDA); RM, rituximab maintenance...Orelabrutinib [18] is licensed only in China...Of note, both acalabrutinib and zanubrutinib induce lower rates of atrial fibrillation, hypertension, and bleeding compared to ibrutinib in randomized studies..."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • PLCG2 • TP53

Advances in the Management of Relapsed/Refractory CLL and Richter Transformation (ICML 2025) - P=N/A, P2, P3 | "BRUIN CLL-321 is a phase 3, registrational study that evaluated pirtobrutinib compared to the investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) [23]...Nemtabrutinib is now being evaluated in the registrational, phase 3 BELLWAVE-010 trial (NCT05947851) for patients with R/R CLL, comparing nemtabrutinib plus venetoclax to venetoclax plus rituximab...An ongoing, open-label, first-in-human phase 1/2 study is evaluating the BTK degrader BGB-16673 as monotherapy in patients with R/R CLL [27, 28]...NX-2127 is an investigational, first-in-class BTK degrader currently being evaluated in a phase 1 trial for patients with relapsed or refractory B-cell malignancies, CLL [29, 30]...NX-5948 is another investigational and more selective BTK degrader in an ongoing Phase 1a/1b clinical trial...This trial aims to establish lisaftoclax plus acalabrutinib as a potential alternative to venetoclax-based BTKi combination..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2L1 • TP53

Title: A phase Ib study evaluating the safety and efficacy of tafasitamab, acalabrutinib, and obinutuzumab (TAO) in previously untreated chronic lymphocytic leukemia and small lymphocytic lymphoma (IWCLL 2025) - No abstract available

Clinical • P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma

Acalabrutinib Monotherapy versus Acalabrutinib plus Obinutuzumab Combination Therapy in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia: A 'Real-World' Study of Efficacy and Safety (IWCLL 2025) - No abstract available

Clinical • Combination therapy • Monotherapy • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Diagnosis and Management of Waldenstrom's Macroglobulinemia (ICML 2025) - P2 | "New or emerging options for patients progressing on c-BTKi include pirtobrutinib, BGB-16673, venetoclax, and sonrotoclax...CXCR4 antagonists such as plerixafor or ulocuplumab can sensitize CXCR4Mut-expressing WM cells to ibrutinib [22-24]...6 BTK Mutations BTKCys481 is the binding site for covalent BTK inhibitors (cBTK-i), including ibrutinib, zanubrutinib, acalabrutinib, orelabrutinib and tirabrutinib...For symptomatic treatment-naïve patients, chemoimmunotherapy with bendamustine and rituximab (Benda-R), dexamethasone, rituximab, and cyclophosphamide (DRC), as well as cBTK-i can be considered...Additional options in second or later relapse include re-use of chemotherapy if a response lasted for > 3 years, alternative chemoimmunotherapy, nucleoside analogs, or everolimus [38]...Zanubrutinib in combination with ixazomib and dexamethasone (ZID) is being investigated in a study in China (NCT04463953) and has shown high levels of response activity and good..."

IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCLAF1 • CXCL12 • FOXO3 • IL10 • IL6 • IRAK4 • MYD88 • PLCG2 • SYK • TNFAIP3 • TRAF3IP2

An assessment of NK and T cell functional immunity in response to vaccination whilst taking acalabrutinib or ibrutinib monotherapy. (IWCLL 2025) - No abstract available

Monotherapy • Hematological Malignancies

BTK inhibitors potently impair platelet aggregation as a class effect independent of BTK specificity or dose in CLL and MCL. (PubMed, J Clin Exp Hematop) - "We investigated whether BTKi impaired platelet aggregation and adhesion in a drug- or dose-dependent manner in patients with CLL and MCL who received ibrutinib, acalabrutinib, or pirtobrutinib. Although the sample size was small, our results suggest the potential of impaired platelet adhesion as a candidate biomarker for estimating bleeding risk in patients receiving BTKi. Second, in BTKi-treated patients requiring anti-platelet agents, BTKi dose reduction may be considered, irrespective of BTK selectivity of the drug or whether aspirin or a P2Y12 receptor inhibitor is used."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology

Ibrutinib and acalabrutinib in the treatment of relapsed/refractory chronic lymphocytic leukemia: a real-world analysis from the Czech Chronic Lymphocytic Leukemia Patients Registry (IWCLL 2025) - No abstract available

Clinical • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Safety Analysis of Fixed-Duration Acalabrutinib-Venetoclax Combinations vs Chemoimmunotherapy: A Post Hoc Analysis From the Phase 3 AMPLIFY Trial (IWCLL 2025) - No abstract available

Clinical • P3 data • Retrospective data • Hematological Malignancies

A Network Meta-Analysis (NMA) of Efficacy of Zanubrutinib versus Fixed-Duration Acalabrutinib Plus Venetoclax in Treatment-naïve (TN) Chronic Lymphocytic Leukemia (CLL) (IWCLL 2025) - No abstract available

Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Number Needed to Treat Analyses of Zanubrutinib vs Acalabrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia (IWCLL 2025) - No abstract available

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Similarities and Differences in Immune Modulation by Acalabrutinib and Zanubrutinib in Chronic Lymphocytic Leukemia (IWCLL 2025) - No abstract available

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

SOUNDTRACK-E: A Phase 1/2 Open-label Multicenter Study to Evaluate the Safety/Efficacy of AZD0486 as Monotherapy or in Combination With Acalabrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (IWCLL 2025) - No abstract available

Clinical • Combination therapy • Monotherapy • P1/2 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma

Comparative Efficacy of Zanubrutinib (ZANU) versus Fixed-Duration Acalabrutinib Plus Venetoclax (AV) for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL): A Matching-Adjusted Indirect Comparison (MAIC) (IWCLL 2025) - No abstract available

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Autoimmune cytopenias in patients with chronic lymphocytic leukemia receiving acalabrutinib treatment. (IWCLL 2025) - No abstract available

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

MAVRiC: A Phase 2 Study of Mutation-Guided Finite-Duration Acalabrutinib Plus Venetoclax for Relapse After Frontline Finite-Duration Covalent Bruton Tyrosine Kinase Inhibitor Plus Venetoclax‒Based Combination Therapy in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (IWCLL 2025) - No abstract available

Clinical • Combination therapy • P2 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma

Chronic Obstructive Pulmonary Disease and Previous Pneumonia have an impact on infectious complications in patients with Chronic Lymphocytic Leukemia treated with Acalabrutinib and Zanubrutinib: a Multicentre SEIFEM Study. (IWCLL 2025) - No abstract available

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Frontline acalabrutinib, lenalidomide and rituximab for advanced stage follicular lymphoma with high tumor burden: phase II trial. (PubMed, Nat Commun) - P2 | "After a median follow-up of 43 months, median PFS and OS were not reached, 2-year PFS rate was 79% and 2-year OS rate was 92%. Here we show that the addition of acalabrutinib to R2 is a safe and effective frontline regimen for FL patients, and further exploration in larger clinical trials is needed."

Journal • P2 data • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology

Management of Relapsed and/or Refractory Chronic Lymphocytic Leukemia. (PubMed, Hematol Oncol Clin North Am) - "Covalent Bruton's tyrosine kinase inhibitors (cBTKis), including acalabrutinib and zanubrutinib, and the BCL2 inhibitor venetoclax are currently sequenced in both front-line and relapsed and/or refractory (R/R) chronic lymphocytic leukemia (CLL). We review treatment options for "double exposed" CLL including venetoclax retreatment, pirtobrutinib, and CAR T-cell therapy with lisocabtagene maraleucel. Emerging treatment options include agents in clinical trials such as BTK degraders and bispecific antibodies."

Journal • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

DYNAMIC CHANGES OF ABSOLUTE CD4 COUNT IN PERIPHERAL BLOOD AS A PREDICTOR OF EFFICACY IN REFRACTORY/RELAPSED DLBCL HARBORING TP53 GENE MUTATIONSTREATED WITH GLOFITAMAB (ICML 2025) - "Despite these treatments (R-CHOP or Pola-R-CHP), relapse or refractory disease remains common...Given the nature of R/R DLBCL, chemo-free regimens included acalabrutinib (100 mg twice daily), zanubrutinib (160 mg twice daily), obutinib (150 mg once daily), sintilimab (200 mg per cycle), and glofitamab in combination with either polatuzumab vedotin (1.8 mg/kg) or lenalidomide (20 mg/day, days 1–14)... Chemo-free regimens incorporating glofitamab demonstrated high efficacy and good tolerability in R/R DLBCL patients with TP53 mutations. Additionally, dynamic changes in absolute CD4 count may serve as a preliminary predictor of glofitamab efficacy."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Lymphoma • Oncology • CD4 • TP53

Frontline acalabrutinib, lenalidomide and rituximab for advanced stage follicular lymphoma with high tumor burden: phase II trial (Nature) - P2 | N=60 | NCT04404088 | "Twenty-four patients with previously untreated FL were included in this phase 2 single arm study (NCT04404088). The most common grade 3-4 adverse events were neutropenia (58%) and liver function test elevation (17%). Best ORR was 100% and best CR rate was 92%. CR30 rate was 65% and POD24 rate was 17%. After a median follow-up of 43 months, median PFS and OS were not reached, 2-year PFS rate was 79% and 2-year OS rate was 92%. Here we show that the addition of acalabrutinib to R2 is a safe and effective frontline regimen for FL patients, and further exploration in larger clinical trials is needed."

P2 data • Follicular Lymphoma