Tipifarnib and Osimertinib in EGFR-mutated Non-Small Cell Lung Cancer

Inclusion Criteria: * Age ≥ 18 years at the time of signing informed consent. * Histologically or cytologically confirmed stage IIIB (locally-advanced) or IV (metastatic) adenocarcinoma of the lung. * The tumor harbors an Ex19del or Ex21-L858R substitution (based on tumor tissue or plasma \[ctDNA\] assessment). * Treatment-naïve for locally advanced/metastatic EGFR-mutated NSCLC and osimertinib treatment-naïve for NSCLC. * ECOG performance score of 0 or 1 with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks. * Measurable disease by RECIST v1.1 that meets the criteria for selection as a target lesion according to RECIST v1.1. * Adequate organ function, as evidenced by the laboratory results. * Other protocol-defined inclusion criteria may apply. Exclusion Criteria: * Treatment with any of the following: 1. Major surgery 2. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug 3. Medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 or uridine 5'-diphospho (UDP)-glucuronosyltransferase (UGT), or inhibitors of breast cancer resistance protein (BCRP). 4. Investigational therapy within 2 weeks of Cycle 1 Day 1 5. Concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of study drug (excluding non-melanoma skin cancer, adjuvant hormonal therapy for breast cancer and hormonal treatment for castration-sensitive prostate cancer) * Spinal cord compression or symptomatic and unstable brain metastases requiring steroids over the last 4 weeks prior. * Evidence of severe or uncontrolled systemic diseases. * Refractory nausea and vomiting, chronic gastrointestinal (GI) diseases, inability to swallow the formulated product, or previous significant bowel resection. * Clinically significant cardiovascular symptoms or disease. * Received treatment for unstable angina within prior year, myocardial infarction within the prior 6 months, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation. * Past medical history of Interstitial Lung Disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. * Other protocol-defined exclusion criteria may apply.