EGFR Mutation Positive Advanced Non Small Cell Lung Cancer, NSCLC (Advanced Non-small Cell Lung Cancer)
Conditions
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.
Interventions
DRUGORIENT-31 regimen
Sintilimab plus bevacizumab plus platinum-doublet chemotherapy
RADIATIONSBRT
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.
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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: 1. 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; 2. 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; 3. 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.
Exclusion criteria
* 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. Withdrawl criteria: * Incorrectly enrolled participants. Those who have not yet received treatment in this study should be immediately withdrawn, and their information will not be included in the study analysis. If treatment has already begun, the investigator should assess the participant's benefit-risk profile and then decide whether to withdraw. If withdrawal is necessary, the participant should exit the study after completing treatment and follow-up and will not be included in the efficacy analysis of this study, but must be included in the safety analysis. * Participants who experience the following during the pre-treatment evaluation phase: new systemic diseases or worsening of existing systemic diseases that meet
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 1 year | The time from the start of drug treatment until death from any cause. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date. |
| Objective Response Rate (ORR) | 1 year | The percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) after treatment, assessed according to the RECIST 1.1 criteria. |
| Treatment-related adverse event (TRAE) | 1 year | Investigator-assessed treatment-related adverse events were recorded and assessed according to CTCAE5.0. |
Countries
China
Contacts
CONTACTZhengfei Zhu, PhD
Outcome results
None listed