Venclexta (venetoclax)

P2, N=10, Terminated, University of Michigan Rogel Cancer Center | N=20 --> 10 | Trial completion date: Jul 2026 --> Aug 2025 | Suspended --> Terminated | Trial primary completion date: Jul 2026 --> Aug 2025; Interim Analysis per Protocol

P2, N=160, Recruiting, Chinese PLA General Hospital | Active, not recruiting --> Recruiting

This work set up a prognostic model for LUAD based on 8 MDRGs, pinpointing promising biomarkers and targets for LUAD treatment.

Moreover, achieving PB WT1 mRNA negativity-regardless of whether this occurred early or later in the therapy།was consistently associated with superior OS and PFS. These findings suggest that PB WT1 mRNA is a sensitive and reliable biomarker for predicting treatment response and long-term outcomes in patients with AML receiving VEN/AZA.

LSC subtyping improves genetic risk stratification and provides subtype-specific therapies: venetoclax-resistant MEP-LSCs respond to BCL-xL inhibitors, whereas MoDe-LSCs are sensitive to MEK1/2 inhibition. Our findings reveal four distinct LSC types with unique vulnerabilities and propose biomarker-guided treatment strategies that complement genetic profiling to overcome venetoclax resistance.

Covalent BTKi (cBTKi) such as ibrutinib, acalabrutinib, and zanubrutinib are effective but alterations in the kinase domain at C481 or BTK gatekeeper residue T474 mutations result in development of resistance...We evaluated the efficacy of a new ncBTKi, docirbrutinib (AS-1763), against 14 BTK mutants, including C481S, T474x, and L528x, as well as gatekeeper and kinase domain double mutants, using biochemical assays, cell-line models, and primary CLL lymphocytes. Docirbrutinib potently inhibited BTK autophosphorylation and mutant BTK-driven cell proliferation, with greater effects than ibrutinib and pirtobrutinib against certain mutants. In treatment-naïve and relapsed/refractory CLL samples, docirbrutinib disrupted B-cell receptor signaling and sensitized cells to apoptosis induced by venetoclax and AZD5991. In a dose-escalation trial (NCT05602363), docirbrutinib decreased CCL3/CCL4 biomarkers and inhibited the B-cell receptor pathway signaling in longitudinal samples from patients with relapsed/refractory CLL. These findings establish docirbrutinib as a pan-mutant ncBTKi with potential to improve outcomes for CLL patients, including those with disease resistant to cBTKi and other ncBTKi.

P1, N=14, Completed, Novartis Pharmaceuticals | Terminated --> Completed

P=N/A, N=40, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Second-generation and third-generation TKIs further improved outcomes by targeting most imatinib-resistant mutations, with ponatinib-based regimens achieving deep molecular responses and long-term survival in most patients. Concurrently, immunotherapies like blinatumomab and CAR-T cells have enabled potent chemotherapy-free strategies, yielding high molecular response rates and challenging the necessity of allo-HSCT for all patients. Current evidence supports reserving allo-HSCT for high-risk patients, while those with sustained minimal residual disease (MRD) negativity may be cured with TKI and immunotherapy alone. Future progress hinges on optimizing combinations, integrating novel agents like asciminib and venetoclax, and leveraging MRD and genomic profiling for precision medicine.

P1, N=101, Completed, PureTech | Recruiting --> Completed

P3, N=531, Active, not recruiting, AbbVie | Trial completion date: Mar 2026 --> Jul 2027 | Trial primary completion date: Mar 2026 --> Jul 2027