An open-label, phase II study of tipifarnib for the treatment of HRAS mutant solid tumors, including squamous cell carcinomas of the head and neck.

TPS2618Background: Tipifarnib is a potent and highly selective inhibitor of farnesyltransferase (FT). FT catalyzes the post-translational attachment of farnesyl groups to signaling proteins that are requisite for localization to the inner cell membrane. While all RAS isoforms (KRAS/NRAS/HRAS) are FT substrates, only HRAS is exclusively dependent upon farnesylation for membrane localization and signaling activation, making HRAS mutant tumors uniquely susceptible to tipifarnib mediated inhibition of FT. Tipifarnib has demonstrated robust activity in HRAS mutant head and neck squamous cell carcinoma (HNSCC) and HRAS mutant squamous non-small cell lung cancer (NSCLC) patient derived xenograft (PDX) models resistant to standard therapies. Methods: This is a multi-institutional, open-label Phase II trial evaluating the efficacy and safety of tipifarnib for pts with HRAS mutant solid tumors. Pts must have either unresectable, locally advanced or metastatic non-hematological malignancies that harbor a missense HR...