lung cancer
Conditions
Interventions
intervention group:adebelizumab combined with bevacizumab and platinum containing chemotherapy
Sponsors
Ruijin Hospital, Shanghai JiaoTong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be eligible for enrollment in this study: (1)Signed informed consent form (ICF). (2)Age between 18 and 75 years, both genders. (3)Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. (4)Histologically or cytologically confirmed locally advanced or metastatic (Stage IIIB-IV) non-squamous non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations ( the International Association for the Study of Lung Cancer [IASLC] 8th edition TNM staging criteria), who have previously failed treatment with at least one EGFR tyrosine kinase inhibitor (EGFR-TKI) and have undergone re-biopsy (histological, cytological, or hematological) with no evidence of EGFR-T790M mutation and PD-L1 tumor proportion score (TPS) >=1%. (5)Measurable target lesions on imaging assessment (CT or MRI) within the 4 weeks prior to enrollment ( RECIST v1.1). (6)Asymptomatic or stable central nervous system (CNS) metastasis patients must meet the following criteria: 1) No radiographic progression for at least 4 weeks post-treatment. 2) Completion of treatment within 4 weeks before enrollment. 3) No requirement for systemic corticosteroid therapy (=10 mg/day prednisone or equivalent) within 2 weeks before enrollment. (7)Expected survival =12 weeks. (8)The function of vital organs within 1 week prior to enrollment met the following criteria: 1) Hematology: white blood cell (WBC) count =3.0×10^9/L, absolute neutrophil count (ANC) =1.5×10^9/L, platelets (PLT) =100×10^9/L, hemoglobin (HGB) =9.0 g/dL. 2) Liver function: aspartate Aminotransferase (AST) =2.5× upper limit of normal (ULN), alanine aminotransferase (ALT) =2.5× ULN, ALT and AST =5× ULN for liver metastases, total bilirubin (TBIL) =1.5× ULN (excluding Gilbert's syndrome =3× ULN), albumin (ALB) =30.0 g/L. 3) Renal function: serum creatinine =1.5× ULN or creatinine clearance rate (CrCl) =50 mL/minute (calculated using the Cockcroft/Gault formula). 4) Coagulation function: international normalized ratio (INR) =1.5, activated partial thromboplastin time (APTT) =1.5× ULN. 5) Others: lipase =1.5× ULN. Patients with lipase >1.5× ULN without clinical or radiological evidence of pancreatitis may be eligible. Amylase =1.5× ULN. Patients with amylase >1.5× ULN without clinical or radiological evidence of pancreatitis may be eligible. Alkaline phosphatase (ALP) =2.5× ULN, patients with bone metastases, ALP =5× ULN. 6) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) =50%. (9) Non-surgical sterilization or fertile female patients must have a negative serum HCG test within 72 hours before the first dose and should not be lactating. They must agree to use appropriate contraception methods (e.g., intrauterine device, contraceptive pills, or condoms, etc.) during the study treatment period and for 3 months after the end of the study treatment. Male patients must agree to use appropriate contraception methods during the study treatment period and for 3 months after the end of the study treatment.
Exclusion criteria
Exclusion criteria: Patients with any of the following will be prohibited from enrolling in this study: (1) Histological or cytological diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or mixed small cell lung cancer (SCLC). (2) Confirmation of ALK fusion, ROS1 fusion, BRAF mutation, ERBB2 (HER2) amplification/mutation, RET rearrangement, MET amplification/MET exon 14 skipping mutation, NTRK fusion positivity, or PD-L1 TPS <1% upon retesting. (3) Patients with EGFR-TKIs as neoadjuvant treatment and no treatment interval =6 months before disease recurrence; except for patients with disease progression during EGFR-TKI neoadjuvant treatment or adjuvant treatment. (4) Patients previously treated with systemic chemotherapy; however, patients previously treated with neoadjuvant, adjuvant chemotherapy, or chemoradiotherapy with no treatment interval =6 months may be eligible. (5) Symptomatic CNS metastasis is not allowed, but enrollment is permitted for asymptomatic or stable CNS involvement for at least 4 weeks after treatment. Patients with chest and symptomatic brain metastatic lesions receiving radiation therapy completed within 4 weeks before enrollment may be eligible and with bone metastases receiving palliative radiation therapy before the first dose of study drug may be eligible. (6) Toxicities from previous anti-tumor treatments other than alopecia and fatigue have not recovered to CTCAE 5.0 = Grade 1 before enrollment. Other toxicities resulting from previous anti-tumor treatments that are expected to be unresolved and have long-term sequelae. (7) Patients with active brain metastases or leptomeningeal metastases. Patients with spinal cord compression that has not been cured or relieved after surgery and/or radiation therapy, or patients with diagnosed spinal cord compression who have compressive incomplete paralysis or complete paralysis after treatment. Patients with liver metastases receiving cryoablation and radiofrequency ablation treatment who still have significant clinical symptoms and abnormal liver function before enrollment. (8) Presence of uncontrollable third-cavity effusions, such as uncontrollable pleural effusion, pericardial effusion, or ascites. (9) Presence of the following heart conditions: 1) NYHA heart function grade III-IV. 2) Unstable angina or electrocardiographic evidence of acute ischemia or myocardial infarction within the past 1 year. 3) Clinically significant ventricular or supraventricular arrhythmias, and conduction system abnormalities (including QTc interval =450 ms for males and =470 ms for females). 4) Clinically significant pericardial and myocardial diseases. (10) Prior receipt of any immune checkpoint therapy, including but not limited to cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitors, PD-1 inhibitors, PD-L1 inhibitors, or other drugs targeting T cells. (11) Use of systemic immunomodulatory agents (including but not limited to thymosin, interferon, or interleukin-2) within 4 weeks before enrollment. (12) Active autoimmune diseases or a history of autoimmune diseases; interstitial pneumonia, drug-induced pneumonia, radiation pneumonia requiring steroid treatment, or active pneumonia with clinical symptoms. (13) Active or uncontrolled severe infections (CTCAE 5.0 = Grade 2) within 2 weeks before enrollment, and/or receipt of antibiotic treatment. (14) Active or treated pulmonary tuberculosis patients. (15) Prior use of anti-angiogenic drugs such as bevacizumab, recombinant human va
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 6-month PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| PFS;ORR;DoR;OS;DCR;safety; | — |
Countries
China
Contacts
Public ContactYi Xiang
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Outcome results
None listed