Venclexta (venetoclax)

P2, N=25, Not yet recruiting, Jennifer Woyach | Initiation date: May 2026 --> Sep 2026

Sonrotoclax demonstrated rapid, durable responses and manageable safety in heavily pretreated patients with R/R MCL, including high-risk subgroups, supporting its further clinical evaluation as an oral therapy for R/R MCL.

P2, N=33, Recruiting, French Innovative Leukemia Organisation | Not yet recruiting --> Recruiting | Trial primary completion date: Jan 2026 --> Dec 2028

P1, N=20, Not yet recruiting, Roswell Park Cancer Institute

Moreover, DEK deletion enhances LSC chemosensitivity to the standard-of-care combination of azacitidine and venetoclax (Aza/Ven), whereas DEK overexpression confers robust chemoresistance. Furthermore, combining CX-4945 with venetoclax promotes LSC apoptosis and represses the PBX3-driven leukemogenic transcriptional program, exhibiting synergistic anti-AML effects both in vitro and in vivo. Collectively, our findings uncover a previously unrecognized phosphorylation event (DEK-4S phosphorylation) that sustains LSCs and establish the CK2-DEK axis as a promising LSC-specific therapeutic strategy for AML.

P1, N=30, Recruiting, OHSU Knight Cancer Institute | Trial completion date: May 2026 --> May 2028 | Trial primary completion date: Mar 2026 --> Mar 2027

Recently, the randomized phase III VERONA study evaluating azacitidine plus venetoclax (VEN) versus azacitidine plus placebo in newly diagnosed HR-MDS showed no difference in overall survival (OS) between the two arms. However, we did not observe a statistically significant difference in OS for HMA/VEN vs. HMA monotherapy (Hazard Ratio [HR]: 0.83; 95% CI: 0.64-1.07; p = 0.15). In subgroup analyses, patients with TP53 wild-type disease (HR: 0.47; 95% CI: 0.29-0.74; p = 0.002) had a significant improvement in OS and those with ≥10% bone marrow blasts (HR: 0.73; 95% CI: 0.53-1.01; p = 0.06) had a trend towards OS benefit with HMA/VEN.

We report that ONC201 and highly potent second generation ClpP agonists (TR-57, TR-107), promote induction of senescence in triple-negative breast cancer (TNBC) cell lines...Finally, the combination of a ClpP agonist with a known senolytic (venetoclax), synergistically increased the amount of cell death observed. In summary, we show that ClpP agonists stably induce an irreversible senescence in a ClpP-dependent manner that synergizes with venetoclax in TNBC cells.

An 8-year-old female patient achieved bone marrow remission with azacitidine and venetoclax and subsequently underwent allogeneic hematopoietic stem cell transplantation from an unrelated umbilical cord blood donor, The conditioning regimen included fludarabine, decitabine, busulfan, and cyclophosphamide, leading to sustained donor engraftment. At the 13-month follow-up, the patient remained in complete hematologic remission without recurrence. This case suggests that allo-HSCT is a feasible curative option for children with high-risk MDS and germline DDX41 predisposition, highlighting the critical importance of screening potential donors for the same mutation.

The patient developed persistent severe thrombocytopenia despite multiple lines of therapy, including corticosteroids, intravenous immunoglobulin, rituximab, splenectomy, and thrombopoietin receptor agonists. Subsequent treatments with ibrutinib and a venetoclax-based regimen failed to improve platelet counts and were discontinued due to worsening cytopenia...Refractory thrombocytopenia in CLL should be approached as a manifestation of complex disease biology rather than an isolated complication. This single observation indicates that in TP53 aberrant cases with multi-mechanism thrombocytopenia, disease-directed targeted therapy may contribute significantly to platelet recovery.

We discuss the biological rationale for combination approaches and summarize the key clinical studies that have defined current practice, including trials evaluating FLT3 inhibitors, gemtuzumab ozogamicin, IDH inhibitors, and venetoclax-based strategies. While genotype-directed strategies-such as FLT3 inhibition-have already demonstrated survival benefit, optimal patient selection, treatment sequencing, and duration remain areas of active investigation. Future progress will likely depend on MRD-driven treatment adaptation, improved understanding of clonal evolution, and the development of rational multi-agent combinations capable of achieving deeper and more durable remissions.

The model was further validated by assessing responses to conventional therapies, including ibrutinib and venetoclax. In conclusion, this 3D spheroid model captures key functional aspects of B-T interactions in CLL, maintaining the dynamic interactions between malignant B cells and their autologous immune components, partially reproducing microenvironmental features, and offering a promising platform for preclinical therapeutic evaluation.