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

NCT06775743 | Recruiting Phase 2

• 1 other identifier: ORBIT
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  The time from the start of drug treatment until the documentation of disease progression or death from any cause, assessed according to the RECIST 1.1 criteria. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date.

  1 year

Secondary Outcomes (3)

• Overall Survival (OS)

  1 year

• Objective Response Rate (ORR)

  1 year

• Treatment-related adverse event (TRAE)

  1 year

Study Arms (1)

SBRT plus ORIENT-31 regimen

EXPERIMENTAL

Drug: ORIENT-31 regimen; Radiation: SBRT

Interventions

SBRT RADIATION

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.

SBRT plus ORIENT-31 regimen

ORIENT-31 regimen DRUG

Sintilimab plus bevacizumab plus platinum-doublet chemotherapy

SBRT plus ORIENT-31 regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients with severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.
• Symptomatic interstitial lung disease or active infectious/non-infectious pneumonia.
• Patients with risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other known risk factors for intestinal perforation.
• History of other malignant tumors.
• Patients with active infections, heart failure, myocardial infarction within the past 6 months, unstable angina, or unstable arrhythmias.
• Physical examination or clinical laboratory findings that the investigator believes may interfere with the results or increase the risk of treatment complications, or other uncontrollable diseases.
• Patients whom the investigator believes currently have lesions requiring palliative radiation therapy.
• Mixed with small cell lung cancer components.
• Nursing or pregnant women.
• Congenital or acquired immunodeficiency diseases including human immunodeficiency virus (HIV), or history of organ transplantation or allogeneic stem cell transplantation.
• Known hepatitis B virus (HBV), hepatitis C virus (HCV), or active tuberculosis infection.
• Patients who have received cancer vaccines or received other vaccines within 4 weeks before starting treatment (Note: Seasonal influenza vaccines are often inactivated vaccines and are allowed, while intranasal preparations are usually live attenuated vaccines and are not allowed).
• Patients who are concurrently using other immunotherapies, chemotherapy drugs, drugs from other clinical trials, or require long-term corticosteroid treatment are not eligible for enrollment.
• Patients with psychiatric disorders, substance abuse, or social issues that affect compliance are not eligible for enrollment after physician review.
• Patients who are allergic to or contraindicated for PD-1 monoclonal antibodies, VEGF monoclonal antibodies, or chemotherapy drugs.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Zhengfei Zhu, PhD

CONTACT

86-18017312901; fuscczzf@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 10, 2025
• First Posted: January 15, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-01

Locations

CN (1)