Toripalimab Combined With Anlotinib and SBRT in Patients With Untreated Brain Metastases of Driven Gene-negative NSCLC

• Status: Recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to explore the efficacy and safety of toripalimab combined with anlotinib and SBRT for non-driver gene mutation untreated brain metastases non-small Cell Lung Cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hubei Cancer Hospital

Criteria

Inclusion Criteria:

1. 18 to 70 years old, no gender limit；

2. Pathologically or cytologically confirmed non-small cell lung cancer, stage IV tumor with initial brain metastasis diagnosed by imaging 2 weeks before enrollment, ≤ 5 intracranial metastases (the patient's primary tumor disease has not received systemic treatment, or the patient has received systemic treatment for more than 6 months, for example, brain metastasis 6 months after postoperative adjuvant chemotherapy for lung cancer);

3. Negative driver genes (EGFR, ALK, ROS1, etc.);

4. ECOG PS score: 0～1;

5. The expected survival time ≥ 3 months;

6. American Radiotherapy Oncology Group (RTOG) neurological status score: 0-1;

7. Intracranial metastases can be measured and evaluated by MRI;

8. Intracranial lesions are suitable for stereotactic radiotherapy based on the linear accelerator;

9. Able to independently complete neurocognitive tests;

10. Able to complete the QOL questionnaire independently;

11. Female subjects with fertility should undergo a urine or serum pregnancy test within 72 hours before receiving the first study drug administration, and prove to be negative, and are willing to use effectively during the test period to 3 months after the last administration Methods of contraception. For male subjects whose partners are women of childbearing age, effective methods of contraception should be used during the trial and within 3 months after the last administration;

12. The functions of important organs meet the following requirements (no blood components and cell growth factors are allowed to be used 2 weeks before the start of the research treatment): Absolute Neutrophil Count (ANC) ≥1.5×10 E+9/L, Hemoglobin (HB) ≥9g/dL, Platelets (PLT)≥90×10 E+9/L, Serum Albumin (ALB)≥2.8g/dL, Total Bilirubin (TBIL) ≤1.5 ULN, ALT、AST≤2.5 UILN(If abnormal liver function is caused by liver metastasis, ≤5 ULN), Serum creatinine sCr≤1.5 ULN, endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula) , Normal thyroid function;

13. The patients joined the study voluntarily and signed an informed consent form (ICF). They had good compliance and cooperated with follow-up.

Exclusion Criteria:

1. Brain metastases are located in the brain stem or other locations, which makes radiotherapy unsuitable;

2. Brain metastasis with hemorrhage or leptomeningeal disease;

3. There is known evidence that patients have mutations in any of the genes above EGFR, ROS-1, ALK;

4. Patients who cannot undergo MRI examination due to metal implants or claustrophobia;

5. Currently participating in interventional clinical research and treatment, or receiving other research drugs or treatment with research equipment within 4 weeks before the first administration;

6. Accept solid organ or blood system transplantation;

7. Past treatment history of CTLA-4, PD-1 or PD-L1 immune checkpoint inhibitors;

8. Suffer from active autoimmune diseases that require hormone or immunomodulatory treatment, such as rheumatoid arthritis, ankylosing spondylitis, type I diabetes, psoriasis, vitiligo, immune-related thyroid dysfunction, etc. (hormone replacement Can be included after treatment is normal);

9. Suffer from acute or chronic infectious diseases, such as hepatitis B, hepatitis C, tuberculosis, and HIV;

10. Allergic to research drug ingredients

11. Active infection or fever of unknown cause occurred during the screening period and before the first administration> 38.5℃ (according to the judgment of the investigator, the subject can be included in the group due to fever caused by the tumor);

12. Suffer from uncontrolled clinical symptoms or diseases of the heart, such as:(1) Heart failure above NYHA II; (2) Unstable angina pectoris; (3) Myocardial infarction occurred within 1 year; (4) Patients with clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention;

13. Suffer from high blood pressure and cannot be well controlled by antihypertensive medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg);

14. Abnormal blood coagulation function (INR>2.0, PT>16s), have a bleeding tendency or are receiving thrombolytic therapy, and allow preventive use of low-dose aspirin and low-molecular-weight heparin;

15. Obvious coughing up blood or hemoptysis of 10ml or more per day in the 2 months before enrollment;

16. Have significant clinically significant bleeding symptoms or have a clear bleeding tendency within 3 months before enrollment;

17. Have received anti-tumor monoclonal antibodies (mAb) within 4 weeks before using the study drug for the first time, or the adverse events caused by the previously received drug have not recovered (ie ≤ grade 1 or reached the baseline level). Note: Except for subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 hair loss, if the subject has undergone major surgery, the toxic reaction and/or complications caused by the surgical intervention must be fully recovered before starting treatment;

18. Live vaccines have been vaccinated within 4 weeks before the first use of the study drug. Inactivated virus vaccines for seasonal influenza and injections are allowed, but live attenuated influenza vaccines for nasal use are not allowed;

19. Past history of head trauma, diseases of the central nervous system and neurological function defects; suffering from intracranial organic diseases with poor drug control effects, such as cerebral infarction, intracranial vascular malformations, etc.;

20. The investigator judged other situations not suitable for inclusion in this study.