Venclexta (venetoclax)

An intensification strategy guided by response and MRD deepened remissions in individuals with residual disease and spared early responders further treatment. This approach merits further study as an alternative to fixed-duration triplet therapy.

The combination of the B-cell lymphoma 2 inhibitor venetoclax with CIT has emerged as a new first-line benchmark with promising response rates and overall survival...Pirtobrutinib has demonstrated responses even in heavily pretreated patients...For R/R disease, novel BTK inhibitors, bispecific antibodies, and cellular therapies are demonstrating substantial efficacy. Ongoing trials investigating combinations of these agents are poised to further transform RT management.

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...By contrast, cells treated with the cell cycle inhibitor and senescence inducer, abemaciclib rapidly regained p-Rb and Myc expression and cell proliferation following washout...Combining a ClpP agonist with a PARP inhibitor (olaparib) produced an additive effect. In summary, we show that ClpP activators stably induce an irreversible senescence in a ClpP-dependent manner that synergizes with venetoclax in TNBC cells.

P2, N=25, Not yet recruiting, First Affiliated Hospital of Zhejiang University

P2/3, N=80, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

These subtypes exhibited distinct drug sensitivities (C1 sensitive to panobinostat, MK-2206, 17-AAG; C2 sensitive to venetoclax) and predicted immunotherapy responses (C1 potentially benefiting more from anti-PD-1)...Crucially, aberrant PKM2 overexpression was linked to imatinib (IM) resistance...To mitigate vMO toxicity, IL3-Lamp2b-engineered exosomes were developed, demonstrating efficient vMO loading, targeted delivery to leukemia cells, potent PKM splicing correction, significant IM resistance reversal, and minimal stromal cell toxicity. This work defines glycolysis-based AML subtypes with therapeutic implications and establishes engineered exosome-delivered vMO as a promising strategy to overcome drug resistance in hyper-glycolytic myeloid leukemia.

P1/2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

Induction chemotherapy (cytarabine and idarubicin) initially achieved remission, but subsequent relapses led to the use of venetoclax and 5-azacytidine, which again resulted in remission. This is the first report that molecularly characterizes the HMBOX1::JAK2 fusion in a de novo AML patient. The identification of this novel alteration adds to the growing and heterogeneous molecular landscape of AML and suggests a potential new avenue for targeted therapy.

Better responses were observed in patients treated with the venetoclax in combination with hypomethylating agent (VEN + HMA) regimen compared to those receiving the '3 + 7' regimens (composite complete remission [CRc], 53.8% vs. 30.2%; p = 0.018)...In conclusion, molecular factors matter in influencing the prognosis of TP53-mutant AML patients. Among them, TP53 mutation sites merit particular attention.

P=N/A, N=15, Completed, Fondazione IRCCS Policlinico San Matteo di Pavia

P=N/A, N=210, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

P=N/A, N=14, Recruiting, Fondazione IRCCS Policlinico San Matteo di Pavia