Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations

Inclusion Criteria: * histologically or cytologically confirmed diagnosis of thyroid cancer (cohort 1) or Squamous Cell Carcinoma head and neck cancer (cohort 2) or Squamous Cell Carcinoma other than HNSCC (cohort 3) for which there is no curative therapy available. * tumor that carries a missense HRAS mutation ith a variant allele frequency (VAF) \> 20%. * Subject consents to provide at least 10 unstained tumor slides for retrospective testing of HRAS gene tumor status * Subject has measurable disease according to RECIST v1.1 and has relapsed or is refractory to prior therapy. * At least 2 weeks since the last systemic therapy or radiotherapy regimen prior to enrolment * ECOG PS 0 or 1 * Acceptable liver function * Acceptable renal function * Acceptable hematologic status • Serum albumin ≥ 3.5 g/dL. Subjects with tumors potentially highly sensitive to tipifarnib (HRAS mutant VAF ≥ 35%) may be enrolled despite a serum albumin \< 3.5 g/dL. Exclusion Criteria: * Prior treatment with an FTase inhibitor * History of relevant coronary heart disease or myocardial infarction within last 3 years, NYHA Grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or serious cardiac arrhythmia requiring medication except atrial fibrillation. * Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 4 weeks prior to Cycle 1 Day 1). Controlled brain metastases that require continuous high dose corticosteroid use within 4 weeks of Day 1. * Non-tolerable \> Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks first dose * Major surgery, other than diagnostic surgery, within 4 weeks prior to first dose, without complete recovery. * Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with HIV, or an active infection with hepatitis B or hepatitis C