Non-small cell lung cancer
Conditions
Interventions
experimental group:Combination therapy with hypofractionated radiotherapy, GM-CSF, and Benmelstobart followed by Benmelstobart plus anlotinib maintenance treatment
Sponsors
The Second Affiliated Hospital of Nanjing Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria will be eligible for this trial: 1. Male or female patients aged between 18 and 75 years; 2. Patients with driver mutation-negative (EGFR/ALK/ROS1 wild-type) advanced/metastatic non-small cell lung cancer who failed prior first-line PD-1/PD-L1 inhibitor therapy (monotherapy or combination therapy [concurrent or sequential] are acceptable); 3. At least one measurable lesion according to RECIST v1.1; 4. Expected survival = 3 months. ECOG performance status: 0-1; 5. Adequate hematological and organ function, defined as meeting all the following criteria: (1). Hematology (No transfusion, blood products, G-CSF, or hematopoietic stimulators within 14 days): 1). Absolute neutrophil count (ANC) >= 1.5 × 10^9/L (1,500/mm³); 2). Platelet count (PLT) >= 80 × 10^9/L (100,000/mm³); 3). Hemoglobin (HB) >= 90 g/L; (2). Renal Function: 1). Serum creatinine (Cr) = 60 mL/min; 2). Urine protein = 28 g/L. (4). Coagulation: 1). International normalized ratio (INR) and activated partial thromboplastin time (APTT) = 50%. 6. Women of childbearing potential must agree to use reliable contraception during the study and for 6 months after study completion, or have a negative pregnancy test (serum or urine) within 7 days before enrollment. All patients (male/female) must be willing to use appropriate contraception during the trial and for 8 weeks (females) / 6 months (males) after the last dose of the investigational product, or be surgically sterilized; 7. Subjects voluntarily participate in the study, sign informed consent, demonstrate good compliance, and agree to follow-up.
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will be excluded from this study: 1. Small cell lung cancer (including mixed small cell and non-small cell lung cancer); squamous cell lung cancer with cavitation, or non-small cell lung cancer with hemoptysis (>20 mL/day); 2. Patients who received >=2 types of PD-1/PD-L1 inhibitor therapy; patients with primary resistance to PD-1/PD-L1 inhibitors. Primary resistance is defined as prior PD-1/PD-L1 inhibitor therapy >=6 weeks with best response of PD or SD =1×10^3 copies/mL; (2). Anti-HCV positive with HCV RNA above ULN; (3). HIV positive. 8. Severe infection within 4 weeks before first dose (including comorbidities requiring hospitalization, sepsis, or severe pneumonia); active infection requiring systemic anti-infective therapy within 2 weeks before first dose (excluding antiviral therapy for HBV/HCV); 9. Any severe acute comorbidity before enrollment: (1). Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage (>=once monthly); (2). Unstable angina and/or congestive heart failure requiring hospitalization within 12 months, vascular disease (e.g., aortic aneurysm or peripheral venous thrombosis requiring surgical repair), or other cardiac impairment affecting drug safety per investigator (e.g., poorly controlled arrhythmia, myocardial infarction/ischemia); (3). Arterial thromboembolism within 6 months, NCI CTCAE grade >=3 venous thromboembolism, TIA, CVA, hypertensive crisis, or hypertensive encephalopathy; (4). Hypertension uncontrolled by monotherapy (SBP>=160 mmHg or DBP>=100 mmHg) or requiring >=2 antihypertensive agents; (5). Renal insufficiency: urine protein >=2+ or 24-hour urinary protein >=1.0 g. 10. Imaging showing tumor invasion around major blood vessels or investigator-judged high risk of fatal hemorrhage due to potential vascular invasion. 11. History of severe bleeding tendency or coagulation dysfunction, including but not limited to: clinically significant hemoptysis (>1 tablespoon/day) within 3 months; clinically significant bleeding symptoms/risk within 4 weeks (e.g., GI bleeding, hemorrhagic gastric ulcer [except surgically resected GI perforation/fistula], non-healing wounds/ulcers/fractures). 12. Major surgery, open biopsy, or significant traumatic injury within 28 days; 13. History of drug abuse with inability to abstain or psychiatric disorders; 14. Known alle
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free Survival;Overall Survival;Disease Control Rate;Safety;Improvement in Quality of Life; | — |
Countries
China
Contacts
Public ContactWang Zhaoxia
The Second Affiliated Hospital of Nanjing Medical University
Outcome results
None listed