P2, N=28, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=12, Not yet recruiting, Nantes University Hospital

P2, N=45, Recruiting, Memorial Sloan Kettering Cancer Center

Venetoclax treatment revealed greater CLL protection within the LN environment than in BM, whereas ibrutinib's mobilizing effect was comparable. This 3D LN model offers an effective ex vivo platform for studying microenvironment-tumour interactions and tissue-specific drug responses.

Pharmacologic PU.1 inhibition with the small molecule DB2313 synergizes with venetoclax in both cell line models and primary patient samples. These findings establish stem-monocytic AML as a transcriptionally and functionally distinct subtype and nominate combined PU.1 and BCL2 inhibition as a rational therapeutic strategy for improving venetoclax response in this patient population.

Furthermore, depletion of BCLAF1 sensitizes AML cells to venetoclax, a clinically relevant BCL-2 inhibitor...Aberrant RNA splicing and metabolic reprogramming are hallmarks of cancer, yet how these processes are mechanistically linked remains unclear. This study identifies BCLAF1 as a key regulator connecting splicing control to amino acid metabolism in acute myeloid leukemia, revealing a previously unrecognized functional vulnerability at the intersection of these pathways.

This study identifies the NLRI pathway as a crucial vulnerability in venetoclax resistance and unveils CHRNB4 as a promising predictive biomarker for treatment response. These results suggest that targeting the NLRI pathway represents a novel strategy for developing next-generation therapies to improve the poor outcomes of current combination treatments.

P1/2, N=31, Recruiting, Jacqueline Garcia, MD | Trial completion date: Dec 2028 --> Dec 2030 | Trial primary completion date: Dec 2026 --> Dec 2028

P1, N=24, Active, not recruiting, BeOne Medicines | Recruiting --> Active, not recruiting

Our results indicate a promising and efficient strategy for the encapsulation and targeted delivery of venetoclax using HFn nanoparticles for AML patients. This delivery system can support co-delivery of various drugs and combination therapy of tumor cells.

P2, N=14, Not yet recruiting, AbbVie

Herein, guided by the structural features of Sorafenib, the selective Bcl-2 inhibitor Venetoclax, and the selective Mcl-1 inhibitor AZD5991, we designed and synthesized a series of novel Sophocarpine-derived analogues bearing a pyridylethyl moiety via a molecular-hybridization strategy. In parallel, a 3D-QSAR (CoMFA) model was constructed to rationalize the structure-activity relationship and to inform further lead optimization. Collectively, these findings identify S6 as a promising Sophocarpine derivative with a putative dual Bcl-2/Mcl-1 targeting profile, with significant anti-HCC activity and potential for preclinical development.