NCT06775743

ORIENT-31 Regimen in Combination With SBRT for EGFR-mutant Metastatic NSCLC After First-line Third-generation EGFR-TKIs

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)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• NSCLC (Advanced Non-small Cell Lung Cancer)
• EGFR Mutation Positive Advanced Non Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	ORIENT-31 regimen	Sintilimab plus bevacizumab plus platinum-doublet chemotherapy
RADIATION	SBRT	Based on the results of the response evaluation, personalized SBRT will be arranged after cycle 4: A. Complete response, CR: continue with maintenance therapy of PD-1 antibody + pemetrexed + VEGF antibody until disease progression, intolerable toxic side effects, or up to two years. B. Stable disease, SD/partial response, PR: if the residual lesions do not exceed three organs and five lesions, and if the investigator deems SBRT feasible, curative-dose stereotactic radiotherapy covering all residual lesions will be administered, with dosing based on the NRG-BR001 study. C. If the residual lesions exceed three organs or five lesions, SBRT (24 Gy/3 Fx) targeting 1-3 selected tumor lesions will be performed, and then continue with maintenance therapy of PD-1 antibody + pemetrexed + VEGF antibody until disease progression. D. Progressive disease, PD: subsequent treatment is conducted according to the standard guidelines.

Timeline

• Start date: 2025-01-15
• Primary completion: 2026-12-31
• Completion: 2027-06-01
• First posted: 2025-01-15
• Last updated: 2026-03-11

Locations

1 site across 1 country: China