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USA-GA-MABLETON Azienda Directories
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Azienda News:
- Venetoclax and Cobimetinib in Relapsed Refractory AML: A Phase 1b Trial
Venetoclax, an oral B-cell lymphoma-2 (BCL-2) inhibitor, 7 has shown limited activity as a monotherapy in R R AML, with a complete remission (CR) CR with incomplete blood count recovery (CRi) rate of 19% 8 Cobimetinib, a small molecule inhibitor of mitogen-activated protein kinase (MAPK) kinases 1 and 2 (MEK1 2), 9 is approved for use in melanoma 10, 11 but has not been evaluated in AML
- Concomitant targeting of BCL2 with venetoclax and MAPK signaling with . . .
The combination of cobimetinib and venetoclax reduces leukemia burden in acute myeloid leukemia models in vivo To test the efficacy of cobimetinib and venetoclax in vivo, we induced leukemia in NSGS mice by injecting the animals with genetically engineered OCI-AML3 Luc GFP cells Leukemia engraftment was confirmed 1 week after injection using BLI
- Venetoclax and Cobimetinib in Relapsed Refractory AML: A Phase . . . - PubMed
Patients and methods: This phase 1b trial evaluated venetoclax, a B-cell lymphoma-2 (BCL-2) inhibitor, plus cobimetinib, a MEK1 2 inhibitor, in patients with relapsed refractory acute myeloid leukemia, ineligible for cytotoxic chemotherapy Two-dimensional dose-escalation was performed for venetoclax dosed daily, and for cobimetinib dosed on
- Cobimetinib Alone and Plus Venetoclax With Without Atezolizumab in . . .
Cobimetinib Alone and Plus Venetoclax With Without Atezolizumab in Patients With Relapsed Refractory Multiple Myeloma Author links open overlay panel Fredrik Schjesvold 1 2, Venetoclax (ven) is a potent, highly selective oral BCL-2 inhibitor 14 Ven monotherapy has demonstrated an acceptable safety profile and anti-myeloma activity,
- Targeting MAPK Signaling Pathway with Cobimetinib (GDC-0973) Enhances . . .
First, anti-leukemia activity of cobimetinib and venetoclax was examined in 18 primary AML samples with diverse genetic alterations The combination significantly enhanced cell death, as compared to the single agent treatment (Fig 1A) Cobimetinib inhibited cell proliferation in the majority of AML cases (34 2 ± 23 7%) and the cell growth
- Cobimetinib Alone and Plus Venetoclax With Without . . . - PubMed
Cobimetinib Alone and Plus Venetoclax With Without Atezolizumab in Patients With Relapsed Refractory Multiple Myeloma Clin Lymphoma Myeloma Leuk 2023 Jan;23 This phase Ib II trial (NCT03312530) evaluated safety and efficacy of cobimetinib (cobi) alone and in combination with venetoclax (ven) with without atezolizumab
- A PHASE IB II MULTI-ARM STUDY WITH VENETOCLAX IN COMBINATION WITH . . .
The primary objective for this study is to assess the safety and tolerability as well as preliminary efficacy of venetoclax in combination with cobimetinib, and venetoclax in combination with idasanutlin in patients with relapsed or refractory acute myeloid leukemia (R R) AML who are not eligible for cytotoxic therapy
- Combination strategies to overcome resistance to the BCL2 inhibitor . . .
A phase I clinical trial of the combination of venetoclax and cobimetinib is currently being conducted on patients with RR AML (NCT02670044) (Table 2) In patients with AML having FLT3 mutations, the corresponding kinase inhibitors can also be used in combination For example, sorafenib inhibits FLT3 and downregulates MCL1 expression It can
- A Study of Cobimetinib Administered as Single Agent and in Combination . . .
Participants will receive cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw
- Venetoclax for AML: changing the treatment paradigm Free
Venetoclax is a specific B-cell lymphoma-2 (BCL-2) inhibitor that can restore activation of apoptosis in malignancies, the survival of which depe express high levels of BCL-2 and causes the suppression of cytokine-induced pERK and pS6 signaling pathways exerted by cobimetinib The combination downregulated MCL-1 and disrupted both BCL-2:BIM
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