Tunlametinib Combination Therapy in KRAS-Mutated Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Who cannot join

• Subjects had received anticancer drugs or investigational drugs within the following time window: 1) Any KRAS G12C mutation inhibitor within 3 years prior to the first dose in this study, including but not limited to Sotorasib (AMG510), Adagrasib (MRTX849), IBI351 (GFH925), Glecirasib (JAB-21822), JDQ443, LY3537982, and GDC-6036; 2) Cituximab or its analogues within 3 years prior to the first dose of this study; 3) Prior MEK inhibitor therapy; 4) Any anticancer therapy (including chemotherapy, targeted therapy, immunotherapy, etc.) or any other investigational drug within 28 days prior to the first dose of this study; 5) Received traditional Chinese patent medicines with explicit antitumor indications in NMPA-approved drug labels within 2 weeks prior to the first dose of this study (including Compound Mylabris Capsules, Kang'ai Injection, Kanglaite Capsules/Injection, Aidi Injection, Yadanzi Oil Injection/ capsules, Xiaoaiping tablets/injection, Huachansu capsules, etc.) within 28 days prior to receiving any anticancer therapy (including chemotherapy, targeted therapy, immunotherapy, etc.) or any other investigational drug therapy in this study; and 6) Received known CYP2D6, CYP3A4, P-gp, and BCRP sensitive substrates with narrow therapeutic windows within 14 days prior to study dosing or within 5 drug half-lives (whichever is longer), unless the participants are approved for inclusion by the researchers and all parties involved..
• NSCLC with other driver gene mutations that have standard treatment drugs (such as EGFR, ALK, BRAF(V600E), HER-2, MET(exon14), ROS1, RET or NTRK1/2/3, etc.) in the past.
• Concurrent primary malignancies are permitted, except in the following circumstances: Other malignancies treated with a single surgical procedure, with complete remission for at least 3 years prior to enrollment; or Untreated basal cell carcinoma or carcinoma in situ (e.g., carcinoma in situ of the skin, breast carcinoma in situ, cervical carcinoma in situ); Prostate cancer requiring only clinical monitoring without treatment.
• Symptomatic or progressively worsening CNS metastases or carcinomatous meningitis. Subjects with a history of brain metastases may be considered for inclusion if clinically stable, provided they meet all of the following criteria: 1) Absence of neurological symptoms, no requirement for corticosteroid therapy, and no indication for radiotherapy; the largest lesion on the most recent pre-enrollment imaging study must have a maximum diameter ≤1.5 cm. 2) Active CNS metastases (e.g., brain or meningeal metastases) are not eligible for enrollment. For subjects with brain metastases who have undergone radiotherapy or local treatment: - If no corticosteroids or antiepileptic drugs were used, asymptomatic status must be maintained for at least 7 days after radiotherapy completion. - If corticosteroids or antiepileptic drugs were used, symptomatic status must be maintained for at least 7 days after discontinuation, and the investigator must assess brain metastases as stable and controlled. 3) For subjects asymptomatic after CNS radiotherapy, corticosteroids must have been discontinued for at least 2 weeks prior to the first study dose.
• Cardiovascular system meeting any of the following criteria: 1) Congestive heart failure at New York Heart Association (NYHA) functional class II or higher; 2) Severe arrhythmia requiring medication; 3) Acute myocardial infarction, severe or unstable angina, coronary artery bypass grafting (CABG), or peripheral artery bypass grafting within 6 months prior to enrollment; 4) Left ventricular ejection fraction (LVEF) <50%; 5) Resting QT interval prolongation (QTcF) as measured by the Fridericia formula, ECG-measured QTcF > 470 ms in females or > 450 ms in males, or presence of risk factors for torsades de pointes, such as investigator-assessed clinically significant hypokalemia, family history of long QT syndrome, or familial arrhythmia history (e.g., Wolff-Parkinson-White syndrome); 6) Uncontrolled hypertension (defined as systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg despite standardized antihypertensive therapy);
• Patients who have experienced arterial or venous thrombotic events within the past 6 months, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, pulmonary embolism, hypertensive crisis, or hypertensive encephalopathy;