The Clinical Trial to Evaluate the Pharmacokinetics and Safety of MRTX849 in Patients With Advanced Solid Tumors

Inclusion Criteria: * 1\. Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation. 2\. Unresectable or metastatic disease. 3\. Available therapy: 1. no available treatment with curative intent, 2. no available standard-of-care treatment or patient is ineligible or declines treatment. 4\. Presence of measurable or non-measurable disease per RECIST 1.1. 5\. Age ≥ 18 years. 6\. Life expectancy of at least 3 months. 7\. Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy, or investigational agent) and radiation therapy discontinued at least 2 weeks before first dose date. 8\. Recovery from the adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia). 9\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 10\. Laboratory values within the ranges below during the screening period: <!-- --> 1. Absolute neutrophil count ≥ 1,000/mm3 (≥ 1.0 x 109/L) 2. Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L) 3. Hemoglobin ≥ 9 g/dL, in the absence of transfusions for at least 2 weeks 4. Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) (if associated with liver metastases or Gilbert's disease, ≤ 3 x ULN) 5. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN (if associated with liver metastases, ≤ 5 x ULN) 6. Creatinine clearance (CrCl) ≥ 60 mL/min. 11\. Women of childbearing potential (WOCBP) or men whose partner is a WOCBP agree to use contraception while participating in this study, and for a period of 6 months following termination of study treatment. 12\. Completed informed consent process, including signing Ethics Committee (EC)-approved informed consent form. 13\. Willing to comply with clinical trial instructions and requirements. Exclusion Criteria: * 1\. Use of the treatment known to cause prolonged corrected QT interval (QTc) or with a known risk of Torsades de Pointes that cannot be switched to alternative treatment within 5 half-lives prior to MRTX849 dosing initiation 2\. Use of any drugs or substances including herbal supplements known or suspected to alter MRTX849 absorption, distribution, metabolism, or excretion: 1. Inhibitors of CYP3A4, CYP2C8, P-glycoprotein (P-gp), or breast cancer resistance protein (BCRP) within 7 days or 5 half-lives, whichever is longer, prior to MRTX849 dosing initiation. 2. Inducers of CYP3A4 or CYP2C8 within 14 days or 5 half-lives, whichever is longer, prior to MRTX849 dosing initiation. 3. Proton-pump inhibitors within 7 days or 5 half-lives, whichever is longer, prior to MRTX849 dosing initiation. 3\. Active brain metastases or carcinomatous meningitis. Patients are eligible if brain metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to study entry without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent). 4\. History of significant hemoptysis or hemorrhage within 4 weeks prior to MRTX849 dosing initiation. 5\. Any of the following cardiac abnormalities: <!-- --> 1. Unstable angina pectoris or myocardial infarction within 6 months prior to MRTX849 dosing initiation. 2. Symptomatic or uncontrolled atrial fibrillation within 6 months prior to MRTX849 dosing initiation. 3. Congestive heart failure ≥ New York Heart Association (NYHA) Class 3 within 6 months prior to MRTX849 dosing initiation. 4. Prolonged QTc interval \> 480 milliseconds. 6\. History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications. 7\. Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B or C infection. Note that the following are permitted: <!-- --> 1. Patients treated for hepatitis C (HCV) with no detectable viral load; 2. Patients treated for HIV with no detectable viral load for at least 1 month prior to study entry while on a stable regimen of agents that are not strong inhibitors of CYP3A4; and 3. Patients with hepatitis B (HBV) receiving prophylaxis against reactivation of hepatitis B (either \[HBsAg-positive with normal ALT and HBV DNA \<2,000 IU/mL or \<10,000 copies/mL\] or \[HBsAg-negative and anti-HBc-positive\]). 8\. Major surgery within 4 weeks prior to MRTX849 dosing initiation. 9\. History of stroke or transient ischemic attack within 6 months prior to MRTX849 dosing initiation. 10\. Known or suspected presence of another malignancy that could be mistaken for the malignancy under study during disease assessments. 11\. Pregnancy. WOCBP must have a negative serum or urine pregnancy test documented within the screening period prior to MRTX849 dosing initiation. 12\. Breast-feeding or planning to breast feed during the study or within 6 months after study treatment with MRTX849. 13\. Any serious illness, uncontrolled intercurrent illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with the patient's participation in the study, or with the interpretation of the results.