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molecules of the month

LUT014

topical BRAF inhibitor (gel) for EGFRi rash

Ph. I in mCRC with EGFRi-related rash

paradoxical activ. of MAPK to counter EGFRi

Cancer Discovery, May 25, 2021

Lutris-Parma, Tel Aviv, IL / MSKCC, NY

LUT014
1 min read

The Lutris-Parma topical BRAF inhibitor, LUT014, is intended to treat rash caused by EGFR inhibitors. Rash is a significant and common side effect of EGFR inhibitor treatment leading to worse quality of life and treatment discontinuations. The rash is on-target, caused by reduced ERK signaling in healthy skin cells. Interestingly, due to paradoxical MAPK activation which increases ERK signaling discussed above for RAF inhibitors, patients who receive a combination of an EGFR inhibitor with systemic BRAF inhibitors have markedly reduced rash. The authors hypothesized that topically treating EGFRi drug-related rash with BRAF inhibitors may reduce the severity of dose-limiting rash, and initiated a 10 patient trial with LUT014. LUT014 was well-tolerated and seems to have a benefit at low concentrations and…


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