Metastatic Non-Small Cell Lung Cancer
Conditions
Interventions
Test group:Cranial Radiotherapy Combined with Fulzerasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer with Brain Metastases
Sponsors
Cancer Hospital of Shandong First Medical University(Shandong Cancer Institute, Shandong Cancer Hospital)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years; 2. Voluntary participation in this study, with the ability to understand and sign the informed consent form; 3. Patients with NSCLC and at least one radiologically confirmed brain metastasis, evaluable by contrast-enhanced MRI; 4. Presence of a KRAS G12C mutation confirmed by genetic testing, without other known actionable driver gene alterations for which targeted therapies are available; 5. Disease progression following prior therapy with anti-PD-1/PD-L1 agents and/or chemotherapy, or intolerance to or refusal of platinum-based chemotherapy and/or anti-PD-1/PD-L1 therapy; 6. At least one measurable lesion according to RECIST version 1.1 criteria; 7. ECOG Performance Status of 0 to 2; 8. Life expectancy >= 6 months; 9. Adequate organ and bone marrow function, defined as: (1) Absolute neutrophil count (ANC) >= 1.2 x 10^9/L, platelet count >= 90 x 10^9/L, and hemoglobin >= 9 g/dL; (2) Adequate hepatic function: total bilirubin (TBIL) < 2.5 x the upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x ULN (or < 5.0 x ULN in case of liver metastases); (3) Adequate renal function: serum creatinine (Cr) <= 1.5 x ULN; (4) Adequate coagulation function: prothrombin time (PT) / activated partial thromboplastin time (APTT) < 1.5 x ULN, and international normalized ratio (INR) < 1.5 (or within the target therapeutic range if on anticoagulation therapy); 10. Toxicities from prior anticancer therapies must have recovered to baseline or Grade <= 2 (except for residual alopecia). Patients with endocrine immune-related adverse events (irAEs) from prior immunotherapy (e.g., hypothyroidism) that are controlled, asymptomatic, and on stable hormone replacement or physiologic corticosteroid doses may be eligible if the investigator assesses no impact on study drug administration or safety evaluation; 11. Ability to swallow and retain oral medication; 12. For patients of childbearing potential or those with partners of childbearing potential, agreement to use highly effective contraception from signing the informed consent form until 6 months after the last dose of study treatment. A negative serum pregnancy test within 7 days prior to initiation of study treatment is required for women of childbearing potential. A blood pregnancy test is required if a urine test is not conclusive; 13. In the investigator's judgment, the patient is capable of good communication, adherence to scheduled follow-up visits, and compliance with the protocol requirements to complete the study.
Exclusion criteria
Exclusion criteria: 1.Prior treatment with any KRAS G12C tyrosine kinase inhibitor; 2.Histologically or cytologically confirmed NSCLC with a small cell component or a predominantly squamous cell carcinoma component; 3.Presence of an EGFR sensitizing mutation, ALK rearrangement, ROS-1 fusion, or any other gene alteration for which an NMPA-approved first-line therapy exists for NSCLC; 4.Contraindication to or inability to undergo contrast-enhanced MRI; 5.Presence of any severe and/or uncontrolled concurrent medical condition that may compromise participation, including but not limited to: 1) Factors affecting drug administration or absorption (e.g., dysphagia, chronic diarrhea, intestinal obstruction). 2) Known hypersensitivity to the study drug or its excipients. 3) History of immunodeficiency (e.g., HIV positive, other acquired or congenital immunodeficiency diseases) or prior organ transplantation. 4) Significant cardiac history, including myocardial infarction or heart failure; or any other cardiac condition deemed unsuitable for participation by the investigator. 5) History of another primary malignancy, except for adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. 6) Clinically significant, symptomatic pleural, peritoneal, or pericardial effusion requiring recurrent drainage. 7) Poorly controlled systemic illnesses despite standard therapy (e.g., hypertension with SBP =160 mmHg or DBP =100 mmHg, diabetes mellitus). 6.Major surgical procedure (excluding procedures like needle biopsy) within 28 days prior to study enrollment, which may interfere with study treatment or evaluation. 7.Pregnancy or lactation; 8.Inability or unwillingness to comply with the study protocol and procedures; 9.Any other condition that, in the investigator's judgment, would make the patient inappropriate for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Intracranial progression-free survival (iPFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Median Overall Survival (OS);Progression-Free Survival (PFS);adverse event;Overall objective response rate (ORR); | — |
Countries
China
Contacts
Public ContactXiangjiao Meng
Cancer Hospital of Shandong First Medical University(Shandong Cancer Institute, Shandong Cancer Hospital)
Outcome results
None listed