Brukinsa (zanubrutinib)

P4, N=33, Recruiting, Shanghai Ninth Peopole's Hospital, Shanghai Jiaotong University School of Medicine; Shanghai Ninth Peopole's Hospital, Shanghai Jiaotong University Sc

P2, N=170, Not yet recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=100, Not yet recruiting, VA Office of Research and Development | Trial completion date: Dec 2029 --> Dec 2030 | Trial primary completion date: Jun 2029 --> Jun 2030

P2, N=19, Not yet recruiting, Ruijin Hospital

To compare the safety and efficacy of zanubrutinib plus rituximab and lenalidomide (ZR2) and R-CHOP-like for elderly patients with newly diagnosed DLBCL, we conducted this single-center prospective study. Patients with gastrointestinal DLBCL have to be monitored closely by abdominal enhanced CT every cycle. Overall, ZR2 chemo-free regimen might be more appropriate for elderly DLBCL patients.

P2, N=80, Not yet recruiting, Navy General Hospital, Beijing

P2, N=80, Not yet recruiting, Navy General Hospital, Beijing

P1, N=119, Completed, BeiGene | Phase classification: P1b --> P1

The first-in-class covalent BTK inhibitor, Ibrutinib, binds to the C481 amino acid residue to block the BTK enzyme and prevent the downstream signaling...To bypass the C481S mutation, non-covalent BTKi, such as Pirtobrutinib, were developed and are active against both wild-type and the C481S mutation...In addition, we discuss the new emerging class of BTK degraders, which utilize the evolution of proteolysis-targeting chimeras (PROTACs) to degrade the BTK protein and constitute an important avenue of overcoming resistance. The moving landscape of resistance to BTKi and the development of new therapeutic strategies highlight the ongoing advances being made towards the pursuit of a cure for B-cell lymphoid malignancies.

P2, N=106, Recruiting, PETHEMA Foundation | Not yet recruiting --> Recruiting

P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025

These data support its use and further evaluation of the BOVen regimen in this high-risk population. NCT03824483.

P4, N=60, Not yet recruiting, AstraZeneca

P2, N=66, Not yet recruiting, Ruijin Hospital

P2, N=42, Recruiting, Sun Yat-sen University

P2, N=42, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2024

P2, N=30, Not yet recruiting, Sun Yat-sen University

P2, N=35, Not yet recruiting, Ruijin Hospital

P2, N=24, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting

P2, N=100, Not yet recruiting, The Lymphoma Academic Research Organisation | Trial completion date: Dec 2031 --> Mar 2032 | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Feb 2028 --> May 2028

P2, N=87, Not yet recruiting, BeiGene

However, bendamustine + rituximab had a more favorable safety profile for grade ⩾3 AEs when compared with ibrutinib (risk ratio 0.62 (95% credible interval 0.40-0.86)), acalabrutinib (0.69 (0.45-0.94)), zanubrutinib (0.64 (0.42-0.91)), and venetoclax + rituximab (0.87 (0.79-0.96)). Our findings showed that venetoclax + rituximab, acalabrutinib, and zanubrutinib have acceptable safety profiles, which indicates that they may be the preferred therapeutic options in the setting of relapsed/refractory CLL. PROSPERO CRD42022304330.

P1/2, N=170, Not yet recruiting, BeiGene

P1/2, N=55, Active, not recruiting, BeiGene | Trial completion date: Sep 2024 --> Jun 2025

P=N/A, N=605, Recruiting, iOMEDICO AG | N=400 --> 605 | Trial completion date: Apr 2027 --> Aug 2028 | Trial primary completion date: Apr 2027 --> Aug 2028

Incidence of atrial fibrillation/flutter was lower with zanubrutinib vs ibrutinib (7.1% vs 17.0%); no cardiac deaths were reported with zanubrutinib vs six cardiac deaths with ibrutinib. This analysis, at 42.5 months median follow-up, demonstrates that zanubrutinib remains more efficacious than ibrutinib with an improved overall safety/tolerability profile.

P2, N=25, Recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland | Not yet recruiting --> Recruiting

P=N/A, N=43, Recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

P2, N=40, Not yet recruiting, The First Affiliated Hospital with Nanjing Medical University

P2, N=177, Completed, BeiGene | Active, not recruiting --> Completed

P1/2, N=97, Completed, BeiGene | Active, not recruiting --> Completed

P2, N=240, Recruiting, Navy General Hospital, Beijing | Not yet recruiting --> Recruiting

The combination of venetoclax (ven), the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has efficacy in CLL. Other secondary endpoints include investigator (INV)-assessed PFS, CRR-INV, uMRD4 rate by flow cytometry, ORR-IRC and -INV, DOR-IRC and -INV, patient-reported outcomes, and safety and tolerability. Recruitment is ongoing.

BGB-10188 showed significant antitumor effects in human B cell lymphoma xenograft models as single agent or in combination with the BTK inhibitor zanubrutinib. BGB-10188 showed significant Treg inhibition in blood but not in colon, along with less drug accumulation in colon compared with idelalisib, which is an approved PI3Kdelta inhibitor with high incidence of gastrointestinal side effects in clinic. In summary, BGB-10188 is a novel PI3Kδ inhibitor with high selectivity, potency and improved safety profile shown in preclinical studies, which is showing the potential as a best-in-class PI3Kδ inhibitor.

P2, N=40, Active, not recruiting, Ruijin Hospital | Trial completion date: Aug 2023 --> Dec 2024

P2, N=42, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | N=30 --> 42

P1, N=274, Recruiting, Prelude Therapeutics | N=104 --> 274 | Trial completion date: Apr 2025 --> Mar 2026 | Trial primary completion date: Apr 2025 --> Nov 2025

P2, N=24, Not yet recruiting, Reid Merryman, MD

However, withthe availability of ibrutinib, acalabrutinib, and zanubrutinib, limited dataexists to guide sequencing of BTKi therapy in the relapsed/refractory setting. Ongoing studies are pushing theenvelope, utilizing targeted drug combinations and minimal residual diseasemarkers as well as receptor tyrosine kinase-like orphan receptor 1 inhibitors, chimericantigen receptor T-cells and novel BTK degraders. However, zanubrutinibrepresents a strong contender in the arsenal of treatment options forrelapsed/refractory CLL.

P2, N=36, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=55, Not yet recruiting, Massachusetts General Hospital

Gene and molecular profiling studies may provide new therapeutic strategies, especially the BCR/TLR/IL-1R/NF-κB signaling pathway in IVLBCL. Here, we treated the hemophagocytic IVLBCL CNS-involved patient with the Bruton tyrosine kinase inhibitor (BTKi) to block NF-κB pathway, and indicated that the second-generation BTKi zanubrutinib-based treatment was feasible and efficient.