non-small cell lung cancer
Conditions
Interventions
Single-Arm Study Phase:Eligible patients will receive Garsorasib (at a starting dose of 600 mg twice daily) in combination with Anlotinib (at a starting dose of 10 mg once daily).
Randomized Controlled Phase: Experimental Group:Patients will receive treatment with Garsorasib in combination with Anlotinib in 21-day cycles.
Garsorasib tablets should be administered orally at 600
Randomized Controlled Phase: Control Group:Patients will receive pemetrexed in combination with carboplatin or cisplatin, plus an investigator's choice of PD-1/PD-L1 inhibitor, in 21-day cycles.
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily participate in the study after full informed consent, sign a written informed consent form (ICF), and be willing and able to comply with the study procedures and requirements stipulated in the protocol. 2. Male or female aged >=18 years and 6 months after the completion of the last treatment. 5. Must provide a written report of KRAS gene mutation testing within 1 year confirming KRAS G12C mutation positivity, issued by a qualified testing institution. 6. At least one target lesion according to RECIST 1.1. Lesions previously treated with radiotherapy or other local regional therapy are not considered target lesions unless they show clear progression after radiotherapy; at baseline screening, lesions must have a long diameter >=10 mm (lymph node lesions must have a short diameter >=15 mm) as measured by CT or MRI, and be suitable for repeated accurate measurement per RECIST v1.1. 7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 8. Adequate organ function meeting the following requirements, with no blood transfusion or use of hematopoietic stimulants within 14 days prior to relevant tests: 1) Platelets (PLT) >=90 × 10?/L; 2) Hemoglobin (HGB) >=90 g/L; 3) Absolute Neutrophil Count (NEUT) >=1.5 × 10?/L; 4) Creatinine =50 mL/min (calculated using the modified Cockcroft-Gault formula); 5) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 months. 10. Female subjects of childbearing age must agree to use contraception (e.g., intrauterine devices, contraceptives, condoms) during the study and for 6 months after termination; serum pregnancy test negative within 7 days before enrollment, and non-lactating. Male subjects must agree to use contraception during the study and for 6 months after termination.
Exclusion criteria
Exclusion criteria: 1. Previous treatment with anti-cancer drugs or investigational products within the following time windows: 1) Any KRAS G12C mutation inhibitor (including but not limited to Sotorasib (AMG510), Adagrasib (MRTX849), IBI351 (GFH925), Glecirasib (JAB-21822), JDQ443, LY3537982, GDC-6036) within 3 years prior to the first dose; 2) Anti-PD-1 or anti-PD-L1 immunotherapies within 3 years prior to the first dose; 3) Small-molecule multi-target tyrosine kinase inhibitors with anti-angiogenic effects (e.g., anlotinib, apatinib) within 3 years prior to the first dose; 4) Any anti-cancer therapy (chemotherapy, targeted therapy, immunotherapy, etc.) or other investigational drugs within 28 days prior to the first dose; 5) Chinese patent medicines with approved anti-tumor indications (including but not limited to Compound Cantharidin Capsules, Kang'ai Injection, Kanglaite Capsules/Injection, Aidi Injection, Brucea Javanica Oil Injection/Capsules, Xiaoaiping Tablets/Injection, Huachansu Capsules) within 2 weeks prior to the first dose. 2. NSCLC with other actionable driver gene mutations with standard treatments (e.g., EGFR, ALK, BRAF (V600E), HER-2, MET (exon14), ROS1, RET, NTRK1/2/3). 3. Concurrent other primary malignancies, except: complete remission for >=3 years without treatment, cured basal cell carcinoma or carcinoma in situ (e.g., skin, breast, cervical), or prostate cancer requiring only clinical monitoring. 4. Symptomatic or progressive central nervous system (CNS) metastases or carcinomatous meningitis. Subjects with a history of brain metastases may be eligible if clinically stable, meeting: 1)No neurological symptoms, no need for corticosteroids, no radiotherapy indication; largest brain metastasis =1.5 cm in long diameter on latest imaging; 2)Asymptomatic newly detected brain metastases during screening are allowed; asymptomatic prior brain metastases must show no CNS progression on two enhanced brain MRI/CT (if MRI is contraindicated) =2 weeks apart, with both scans =2 weeks after last brain radiotherapy (if applicable); symptomatic CNS metastases may be eligible if clinically stable after radiotherapy/surgery and meeting other criteria; 3) =4-week interval between CNS metastasis surgery and first dose; 4) Corticosteroids discontinued for =2 weeks before first dose in asymptomatic post-radiotherapy subjects. 5. Any cardiovascular condition: 1) New York Heart Association (NYHA) class II or higher congestive heart failure; 2)Severe arrhythmias requiring medication; 3) Acute myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass grafting within 6 months prior to enrollment; 4) Left ventricular ejection fraction (LVEF) 470 ms in females or >450 ms in males, or risk factors for torsades de pointes (e.g., clinically significant hypokalemia, family history of long QT syndrome or arrhythmias); 6) Uncontrolled hypertension (systolic =150 mmHg and/or diastolic =100 mmHg despite standard treatment). 6. Arterial/venous thromboembolic events (e.g., cerebrovascular accident, deep vein thrombosis, pulmonary embolism), hypertensive crisis, or hypertensive encephalopathy within 6 months. 7. History of epilepsy. 8. Superior vena cava syndrome. 9. History of steroid-treated interstitial lung disease, radiation pneumonitis, immune-related pneumonia; active non-infectious pneumonia (interstitial changes) at screening; active pulmonary tuberculosis, pneumoconiosis,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Single-Arm Study Phase: Objective Response Rate (ORR);Randomized Controlled Phase: Progression-Free Survival (PFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival;Duration of Response;Disease Control Rate;Time to Response ; | — |
Countries
China
Contacts
Public ContactZhong Hua
Shanghai Chest Hospital
Outcome results
None listed