Chemotherapy, Immunotherapy, Non Small Cell Lung Cancer, Radiotherapy
Conditions
Brief summary
Chemotherapy combined with immunotherapy has become the first-line standard treatment regimen for metastatic non-small cell lung cancer (NSCLC). QL1706 is an antibody that can simultaneously block the CTLA-4 and PD-1. In a phase II clinical study, when QL1706 was combined with chemotherapy for first-line treatment of metastatic NSCLC, the median progression-free survival (mPFS) was 6.8 months and the objective response rate (ORR) was 45% at a median follow-up time of 12.6 months (range, 0.4-15.2 months). Radiotherapy is one of the commonly used local treatment modalities for tumors, which has a synergistic effect with immunotherapy, can enhance the response to immunotherapy, and trigger the abscopal effect. Quad shot radiotherapy is a periodic pulsed hypofractionated radiotherapy, with a specific mode as follows: 2 fractions per day, with an interval of more than 6 hours between the two fractions, for 2 consecutive days, with a total dose of 14-14.8 Gy. This regimen can be repeated every 3-4 weeks for a total of 3 cycles, with a total treatment dose of approximately 44-48 Gy, and it can be used for palliative treatment of various advanced tumors. This project intends to explore whether the addition of Quad shot radiotherapy to QL1706 combined with chemotherapy can improve local and systemic tumor control rates, prolong patients' PFS, and evaluate the safety of the combined therapy in treatment-naive patients with metastatic NSCLC.
Interventions
RADIATIONQuad shot
Intensity-modulated radiotherapy (IMRT) technique is adopted, and only partial lesions (as determined by the investigator) receive Quad shot radiotherapy. Only the gross tumor volume (GTV) is irradiated, with no prophylactic irradiation of lymph nodes. The irradiation dose for the planning gross tumor volume (PGTV) is 14.8 Gy in 4 fractions, administered twice daily (bid), with an interval of more than 6 hours between each irradiation. The treatment is repeated every 3 weeks for a total of 3 cycles.
DRUGChemotherapy
For patients with lung squamous cell carcinoma, TC regimen chemotherapy combined with QL1706 is administered on days 1, 22, 43, and 64, respectively. The specific TC chemotherapy regimen is as follows: nab-paclitaxel 260 mg/m², intravenous infusion; carboplatin at an AUC of 5, with the total dose (mg) calculated as AUC × (GFR + 25), where GFR refers to glomerular filtration rate, administered via intravenous infusion. For patients with lung adenocarcinoma, PC regimen chemotherapy combined with QL1706 is administered on days 1, 22, 43, and 64, respectively. The specific PC chemotherapy regimen is as follows: pemetrexed 500 mg/m², intravenous infusion; carboplatin at an AUC of 5, with the total dose (mg) calculated as AUC × (GFR + 25), where GFR refers to glomerular filtration rate, administered via intravenous infusion.
DRUGImmune Checkpoint Inhibitors
The specific treatment regimen for QL1706 is as follows: QL1706 (5 mg/kg) via intravenous infusion.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed age: 18-75 years; 2. Histologically or cytologically diagnosed as lung squamous cell carcinoma or lung adenocarcinoma; 3. Staged as stage IV (T1-4NxM1) according to the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) Cancer Staging System (9th edition), with at least 2 evaluable lesions, including one distant metastatic lesion; 4. Driver gene-negative; 5. ECOG performance status: 0-1; 6. Normal bone marrow function: white blood cell count \> 4×10⁹/L, hemoglobin concentration \> 90 g/L, platelet count \> 100×10⁹/L; 7. Normal liver and kidney function: total bilirubin ≤ 1.5×upper limit of normal (ULN); aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5×ULN; alkaline phosphatase (ALP) ≤ 2.5×ULN; creatinine clearance ≥ 60 mL/min; 8. Normal results of thyroid function, amylase, lipase, pituitary function, inflammatory/infectious markers, myocardial enzymes, and electrocardiogram (ECG). For patients aged \> 50 years with a smoking history, normal pulmonary function test results are required. For patients with abnormal ECG or a history of cardiovascular disease (that does not meet the
Exclusion criteria
listed in item 7), additional myocardial function tests and echocardiography are required, with normal results; 9. Patients have signed the informed consent form and are willing and able to comply with follow-up, treatment, laboratory tests, and other study requirements as specified in the study schedule; 10. Female subjects of childbearing potential must agree to use reliable contraceptive methods (e.g., condoms, regularly used contraceptives as prescribed by a physician) from screening until 1 year after treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate | 1 year |
Contacts
Primary ContactKunyu Yang
Outcome results
None listed