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dabrafenib + LTT462 + TNO155
- Development stage
- Unknown
- Lead developer
- Novartis
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
**dabrafenib + LTT462 + TNO155** is an investigational combination of three small-molecule inhibitors used in clinical trials for adult patients with advanced or metastatic BRAF V600 mutant colorectal cancer. **Dabrafenib** is a selective BRAF inhibitor, **LTT462** is a selective ERK1/2 inhibitor, and **TNO155** is a selective SHP2 inhibitor. The combination is designed to enhance suppression of the MAPK pathway at multiple nodes: dabrafenib inhibits mutant BRAF, LTT462 inhibits downstream ERK signaling, and TNO155 targets SHP2 which transduces signals from receptor tyrosine kinases to the MAPK pathway. The rationale is to overcome resistance and feedback reactivation that can occur with single-agent or dual blockade, aiming for deeper and more sustained pathway inhibition and better antitumor activity[3][4][5][6][9]. The combination is being evaluated in phase 1 trials for safety, tolerability, and recommended dosing[3][5].
- Brand names
- Tafinlar (dabrafenib)
- Other names
- dabrafenib + LTT462 + TNO155
02
Targets
PTPN11 (Tyrosine-protein phosphatase non-receptor type 11)MAPK3 (Mitogen-activated protein kinase 1)BRAF (B-Raf proto-oncogene, serine/threonine kinase)
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