This study is to determine the maximum tolerated dose (MTD) of MRTX849 using one or more dosing regimens. The regimens includ using MRTX849 or in combination with Afatinib, Cetuximab, or Pembrolizumab. The study will also look at how it can be tolerated MRTX849 when its taken with food.

If you take part in this research, your major responsibilities will include: • Keep your study appointments and complete all study assessments. If you cannot keep an appointment, please contact study personnel (your study doctor or study staff) as soon as possible to schedule a new appointment. • Inform your study personnel about any symptoms, changes in medications, doctor's or nurse's appointments, or hospital admissions that you may have had. • Agree to not participate in any other clinical research study • Inform study personnel if you believe you or your partner might be pregnant • Inform study personnel if you change your mind about participating in the study. • Inform your other doctors that you are taking part in this study. • Avoid grapefruit and grapefruit juice. • Avoid herbal medications and preparations including but not limited to St. John’s wort, Kava, turmeric/curcumin, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe (yohimbine), saw palmetto, and ginseng. • Avoid medications that are processed by liver enzymes, your doctor will counsel you on these. • Avoid medications known to have risk of changing the electrical activity in the heart, your doctor will council you on these. • For your safety, you must tell the study doctor or nurse about all the prescription drugs, herbal products, over-the-counter drugs (OTC), vitamins and other supplements you are taking. Check with the study doctor before starting any new medicines (including prescription, OTC drugs, vitamins and herbal supplements) or changing doses of medications that you are already taking.