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encorafenib + binimetinib + buparlisib
- Development stage
- Discontinued
- Lead developer
- Pfizer
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
**Encorafenib + binimetinib + buparlisib** is an experimental **triple combination therapy** for BRAF-mutant cancers. It consists of encorafenib, a potent small molecule inhibitor of BRAF V600E/K-mutant kinases; binimetinib, a reversible small molecule inhibitor of MEK1/2; and buparlisib, a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor. The combination targets sequential signaling nodes in the MAPK and PI3K pathways to simultaneously inhibit tumor proliferation, survival, and resistance mechanisms. The primary indication investigated for this regimen has been advanced/metastatic melanoma, with trials exploring its use for patients who have progressed on previous BRAF/MEK inhibitor therapy. The triplet was studied in phase I/II arms (e.g., LOGIC-2 study), but the buparlisib arm was closed early due to significant drug-drug interactions with encorafenib. Clinical development of the combination was therefore not pursued further for melanoma.
- Brand names
- Braftovi + Mektovi + buparlisib
- Other names
- encorafenib + binimetinib + buparlisib
02
Targets
PI3K (Phosphoinositide-3-kinase regulatory subunit 6)BRAF (B-Raf proto-oncogene, serine/threonine kinase)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)RAF1 (c-Raf-1 (Y340D/Y341D))
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