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lgh447 + alpelisib
- Development stage
- Discontinued
- Lead developer
- Novartis
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
LGH447 + alpelisib is an experimental oral combination of two small molecule inhibitors developed for the treatment of cancer, primarily investigated in relapsed and refractory multiple myeloma. LGH447 (also known as PIM447) is a pan-PIM kinase inhibitor, targeting serine/threonine kinases (PIM1, PIM2, PIM3) involved in cell growth and survival. Alpelisib (also known as BYL719) is a phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitor, targeting the PI3K/AKT signaling pathway important in cancer cell proliferation and survival. This combination was investigated due to a biological rationale for dual pathway inhibition, but the main phase Ib/II study for relapsed/refractory multiple myeloma was terminated early due to lack of clinical tolerability and dose-limiting toxicities (notably thrombocytopenia). There is interest in PI3K/PIM overlap in other cancers, but clinical evidence remains limited to early-phase study and preclinical synergy data[1][2][4].
- Other names
- lgh447 + byl719
02
Targets
PIM2 (Proto-oncogene serine/threonine-protein kinase Pim2)PIM1 (Proviral integration site for moloney murine leukemia virus kinase 1)PIM3 (Proviral integration site for Moloney murine leukemia virus kinase 3)PIK3CA (Phosphoinositide 3-kinase alpha)
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