Lung Neoplasms, Non Small Cell Lung Cancer
Conditions
Keywords
Non-small-cell lung cancer, Stereotactic radiation therapy, Envafolimab, Endostar, Immunotherapy, Anti-angiogenic therapy, Phase II clinical trial
Brief summary
This is a prospective, single-arm phase II clinical study. It intends to evaluate the efficacy and safety of stereotactic radiation therapy (SRT) combined with envafolimab and endostar as first-line treatment in stage IV non-small cell lung cancer (NSCLC) patients without actionable EGFR/ALK/ROS1 driver gene alterations and with PD-L1 TPS ≥ 1%. A total of 61 eligible participants will receive combination treatment of stereotactic radiotherapy, envafolimab and endostar. Tumor response will be evaluated every 6 weeks according to RECIST v1.1, and treatment-related adverse events will be monitored based on NCI-CTCAE v5.0. The treatment will continue until disease progression, patient withdrawal, loss of follow-up or death.
Detailed description
This prospective multi-center single-arm phase II trial focuses on unresectable stage IV NSCLC patients with negative driver genes and positive PD-L1 expression (TPS ≥1%). Eligible subjects are treatment-naive patients or recurrent cases after adjuvant chemotherapy. Patients will receive stereotactic body radiation therapy targeting 1 to 5 metastatic lesions with a dose of 30-50 Gy in 5-10 fractions. Within 1 to 7 days after radiotherapy, patients will receive 300 mg envafolimab subcutaneously on day 1 and 210 mg endostar continuous intravenous pumping on days 1-3 of each 3-week cycle. The overall clinical efficacy and safety profiles of this combined regimen will be systematically observed.
Interventions
RADIATIONStereotactic Radiation Therapy
Stereotactic radiotherapy delivered to 1-5 metastatic lesions, with a total dose of 30-50 Gy in 5-10 fractions. Lesions are selected based on larger volume, symptomatic status, or visceral location; treatment of all metastatic lesions is not required.
DRUGEnvafolimab
300 mg administered by subcutaneous injection on Day 1 of each 3-week treatment cycle, initiated within 1-7 days after completion of radiotherapy.
DRUGEndostar
210 mg administered by continuous intravenous pumping on Days 1-3 of each 3-week treatment cycle, initiated within 1-7 days after completion of radiotherapy.
Sponsors
The First People's Hospital of Lianyungang
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects voluntarily participate in this study, sign the written informed consent form, and demonstrate good compliance. 2. Aged 18-80 years old at the time of signing informed consent, male or female. 3. Histologically confirmed stage IV non-small-cell lung cancer (NSCLC) according to the 8th IASLC/AJCC TNM staging system, with negative actionable driver gene alterations (EGFR/ALK/ROS1), and no prior systemic anti-cancer treatment. 4. Provide archived tumor tissue samples or newly obtained core/excisional biopsy specimens from tumor lesions which have not received prior anti-tumor therapy or radiotherapy. Formalin-fixed paraffin-embedded (FFPE) tissue blocks are preferred over slides; newly-obtained biopsy samples are preferred over archived tissues. PD-L1 expression ≥1% is confirmed by immunohistochemistry. For subjects without newly-obtained tissue, 5-8 slices of 3-5 μm paraffin sections of archived tissue collected within 2 years before enrollment are acceptable. 5. Have at least one radiologically measurable lesion per RECIST version 1.1: target lesion with longest diameter ≥10 mm on CT/MRI, or pathologically enlarged lymph node with short-axis diameter ≥15 mm on CT scan. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 7. Expected survival time ≥ 3 months. 8. Treatment-naive patients without previous systemic anti-tumor therapy (including radiotherapy, chemotherapy, targeted or immunotherapy), or patients with disease recurrence more than 6 months after completion of postoperative adjuvant chemotherapy. 9. Adequate organ and bone marrow function confirmed by laboratory tests obtained within 7 days before enrollment. No blood product transfusion, growth factors, albumin or other corrective medications are permitted within 14 days prior to laboratory assessment: 1\) Hematology: absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count (PLT) ≥75×10⁹/L, hemoglobin (HGB) ≥90 g/L (no transfusion or erythropoietin-dependency within 14 days); 2) Liver function: total bilirubin (TBIL) ≤2×ULN; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤5×ULN; serum albumin ≥28 g/L; alkaline phosphatase (ALP) ≤5×ULN; 3) Renal function: serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50 mL/min using Cockcroft-Gault formula; urine protein \<2+ on urinalysis. For baseline urine protein ≥2+, 24-hour urine protein quantification must be \<1 g. 4\) Coagulation function: international normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN. For subjects receiving anticoagulants, INR within the therapeutic target range of anticoagulation is acceptable. 10\. For women of child-bearing potential, negative urine or serum pregnancy test within 3 days prior to first study drug administration. 11\. Tissue samples must be available for biomarker (e.g. PD-L1) analysis. Newly-obtained specimens are preferred; archived paraffin sections obtained within 2 years before enrollment are allowed if fresh tissue cannot be acquired.
Exclusion criteria
1. Tumor invades major blood vessels on CT/MRI, or judged to carry high risk of invading critical vessels and causing fatal hemorrhage during study treatment. 2. Currently participating in another interventional clinical trial, or received investigational drug/device within 4 weeks before first study drug administration. 3. Received anti-tumor Chinese patent medicine or immunomodulatory agents (such as thymosin, interferon, interleukin) within 2 weeks prior to first dose; or underwent major surgical operation within 3 weeks before first dose. 4. Active hemoptysis requiring clinical intervention, active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or peritoneal metastasis. 5. Any bleeding diathesis regardless of severity; any bleeding/hemorrhagic event ≥ CTCAE grade 3 within 4 weeks before enrollment; unhealed wound, ulcer or fracture. 6. New York Heart Association (NYHA) class III-IV congestive heart failure, or uncontrolled clinically significant arrhythmia. 7. History of arterial thrombosis, embolism or ischemic events within 6 months before study entry, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack. 8. Known hypersensitivity to any study drug. 9. Require chronic systemic corticosteroid therapy. Intermittent bronchodilators, inhaled corticosteroids for COPD/asthma, or local corticosteroid injection are permitted. 10. Symptomatic central nervous system (CNS) metastases. Patients with asymptomatic or treated-stable brain metastases may be enrolled only if all of the following criteria are met: measurable extracranial lesion; no midbrain, pons, cerebellum, meningeal, medulla oblongata or spinal cord metastasis; clinically stable for at least 2 weeks; systemic steroid discontinued at least 3 days before first study drug dose. 11. Active infection requiring treatment, or systemic anti-infective medication administered within 1 week before first dose. Subjects have not sufficiently recovered from toxicity/complications induced by prior interventions (≤ grade 1 or return to baseline, excluding fatigue and alopecia). 12. Known human immunodeficiency virus (HIV-1/2 antibody positive). 13. Untreated active hepatitis B (HBsAg positive with HBV-DNA above local laboratory upper limit of normal). Subjects with HBV viral load \<1000 copies/mL (200 IU/mL) are eligible and should receive anti-HBV prophylaxis during study therapy to prevent viral reactivation. Anti-HBc positive, HBsAg negative, anti-HBs negative and HBV-DNA negative subjects do not require prophylactic anti-HBV therapy but need close monitoring for viral reactivation. 14. Active hepatitis C infection (HCV-Ab positive with HCV-RNA above assay lower limit). 15. Received live-attenuated vaccine within 30 days before Cycle 1 Day 1. Seasonal inactivated injectable influenza vaccine within 30 days before first dose is allowed; intranasal live-attenuated influenza vaccine is prohibited. 16. Pregnant or breastfeeding women. 17. Medical history, disease condition, treatment or laboratory abnormality that may interfere with study results or prevent full participation in the trial; or other conditions judged by the investigator to render the subject unsuitable for enrollment or associated with potential safety risks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From treatment initiation up to 24 weeks | Percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST version 1.1. CR and PR must be confirmed by subsequent tumor assessment during the study. |
| Incidence of Treatment-Related Adverse Events | From first study treatment to 90 days after last study treatment | Number and severity of treatment-related adverse events, laboratory abnormalities, vital sign and electrocardiogram changes, evaluated according to NCI-CTCAE version 5.0. Safety analyses will be performed in the safety set. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From treatment start until progression or death, up to 36 months | Time from treatment initiation to first documented radiological disease progression (per RECIST v1.1, investigator-assessed) or death from any cause, whichever occurs first. Participants without progression or death will be censored at the date of last valid tumor assessment. |
| Overall Survival (OS) | From treatment start until death from any cause, up to 48 months | Time from treatment initiation to death due to any cause. |
| Disease Control Rate (DCR) | From treatment initiation up to 24 weeks | Percentage of participants achieving complete response (CR), partial response (PR), or stable disease (SD), as assessed by the investigator according to RECIST version 1.1. |
| Duration Of Response (DOR) | From first confirmed response until progression or death, up to 36 months | Time interval from the first documented objective tumor response until disease progression or death from any cause, whichever occurs first. |
Countries
China
Contacts
CONTACTXiaodong Jiang, MD
Outcome results
None listed