Calquence (acalabrutinib)

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

This study is the first to report real-world evidence on treatment choice in first-line CLL and highlight two distinct groups of patients.

Acalabrutinib-based regimens, either as monotherapy or combined with obinutuzumab, emerged as the most effective strategies for progression-free survival, followed by other BTK inhibitors and venetoclax-based combinations. Chlorambucil- and Fludarabine-containing regimens ranked lowest...Overall, heterogeneity was low, model fit was robust, and no statistical evidence was detected. These findings support targeted agents as the preferred first-line treatment for IGHV-U CLL and provide a quantitative framework to guide regimen selection while highlighting the need for head-to-head trials and long-term follow-up to optimize treatment sequencing.

P2, N=40, Recruiting, Massachusetts General Hospital | Trial completion date: Mar 2027 --> Mar 2029 | Trial primary completion date: Mar 2026 --> Mar 2028

P1/2, N=408, Recruiting, AstraZeneca | N=276 --> 408 | Trial completion date: Feb 2028 --> Jun 2029

This study provides a pragmatic, consensus-driven framework for FD BTKi-venetoclax therapy in CLL, emphasizing patient selection and logistical feasibility. The work lays the groundwork for more rigorous evaluation of human-AI collaboration in the still-complex landscape of first-line CLL therapy.

P2, N=55, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

Aberrant B cell receptor signaling occurs in several B cell neoplasms including follicular lymphoma (treated with zanubrutinib, a BTK inhibitor), mantle cell lymphoma (acalabrutinib, pirtobrutinib, zanubrutinib), marginal zone lymphoma (zanubrutinib), chronic lymphocytic leukemia and small lymphocytic lymphoma (ibrutinib, acalabrutinib, zanubrutinib, pirtobrutinib), and Waldenström macroglobulinemia (ibrutinib, zanubrutinib)...Pirtobrutinib fails to form a covalent bond and is a reversible BTK inhibitor. The FDA-approvals of rilzabrutinib and remibrutinib (2025) represent the first nononcologic authorizations for BTK antagonists.

P=N/A, N=120, Recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

To date, ten abstracts or published manuscripts have reported on venetoclax retreatment, as continuous monotherapy or with FD/MRD guided combinations with anti-CD20 monoclonal antibodies (rituximab, obinutuzumab) or covalent Bruton tyrosine kinase inhibitors (ibrutinib, acalabrutinib). Median progression-free survival, when available, ranged from 23 to 58 months. Optimal patient selection remains to be defined, but the depth of the initial venetoclax response and time to progression from last venetoclax exposure may predict rechallenge efficacy and are incorporated in new clinical trial criteria allowing previous FD venetoclax treatment.

Among them, 35 patients received BTKi (zanubrutinib, orelabrutinib, acalabrutinib) combined with R-CHOP (BTKi + R-CHOP group) , and 60 received R-CHOP regimen alone (R-CHOP group) . Grade ≥ 3 adverse events primarily included neutropenia (28.6% ) and pulmonary infection (14.3% ) ; no fatal bleeding or cardiovascular events occurred. BTKi combined with R-CHOP significantly improved response rates and survival in patients with DE-DLBCL, with manageable safety.

P1, N=25, Active, not recruiting, Washington University School of Medicine | Trial completion date: Oct 2027 --> May 2028 | Trial primary completion date: Jan 2026 --> Aug 2026