ORIENT-31 Regimen (Sintilimab Plus Bevacizumab Plus Platinum-doublet Chemotherapy) in Combination With Stereotactic Radiotherapy in EGFR-mutant Metastatic Non-small Cell Lung Cancer After First-line Third-generation EGFR Tyrosine Kinase Inhibitors (ORBIT Study)
The goal of this prospective study is to explore the safety and preliminary efficacy of stereotactic body radiotherapy (SBRT) combined with ORIENT-31 regimen (Sintilimab plus bevacizumab plus platinum-doublet chemotherapy) for advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients who failed first-line third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment. Participants will first receive the standard four-drug combination therapy: PD-1 antibody + vascular endothelial growth factor (VEGF) antibody + platinum + pemetrexed. The efficacy will be evaluated every two courses. According to the efficacy evaluation results, personalized SBRT was be administered.
• ECOG performance status score of 0-1;
• Histologically or cytologically confirmed stage IV primary non-small cell lung cancer;
• EGFR-sensitive mutations (L858R, 19del);
• Resistance to first-line treatment with third-generation EGFR-TKIs;
• At least one measurable lesion;
• Patients with brain metastases may be included, but they must be asymptomatic neurologically and have stable lesions without the need for systemic corticosteroid treatment;
• Men and women of reproductive age agree to contraception during the trial (surgical sterilization or oral contraceptives/intrauterine device + condoms);
• Life expectancy ≥ 3 months;
• Within one week before enrollment, organ function levels must meet the following criteria:
‣ Bone marrow function: Hemoglobin ≥ 80 g/L, white blood cell count ≥ 4.0 × 10\^9/L or neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L;
⁃ Liver: Serum total bilirubin level ≤ 1.5 times the upper limit of normal, and when serum total bilirubin level \> 1.5 times the upper limit of normal, direct bilirubin level must be ≤ the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal;
⁃ Kidney: Serum creatinine level \< 1.5 times the upper limit of normal or creatinine clearance rate ≥ 50 ml/min, blood urea nitrogen ≤ 200 mg/L; serum albumin ≥ 30 g/L;
• Patients must have the capacity to understand and voluntarily sign the informed consent form.