Study Name:
Phase II study of Cadonilimab combined with bevacizumab and chemotherapy for advanced nonsquamous non-small cell lung cancer patients with untreated brain metastases Purpose of research MAIN OBJECTIVE: Total response rate (ORR) Secondary purposes: progression-free survival (PFS), intracranial PFS (iPFS), overall survival (OS), Quality of Life (QoL) and safety Exploratory Objective: To explore the potential evolutionary mechanism of brain metastasis of lung cancer and the difference of immune microenvironment between primary focus and metastatic focus.
Design type: Intervention research Subjects: Non-squamous NSCLC in advanced stage of untreated brain metastasis Sample size: 36 cases Statistical analysis method: This cohort was a one-arm test, using Simon-Minimax two-stage design, assuming that the ORR rate was 20% under the ineffective hypothesis and 40% under the hypothesis that the drug was considered effective. The degree of assurance is 0.8, the test level α is set to 0.05, and the sample size estimation result is a total sample of 33 cases. Eighteen subjects who meet the admission criteria are planned to be enrolled first. If 4 patients have CR or PR, they will continue to be enrolled until 33 patients are reached. Only when more than 10 patients in the total sample reach CR or PR can the study reach the main endpoint. Considering the shedding rate of 10%, the sample size of this study is estimated to be 36 cases. Data were collected from the first day of treatment to the death of the patient or the last follow-up. All rate estimates were evaluated by Kaplan-Meier model (SPSS, version 25.0). Univariate analysis and multivariate analysis of Cox regression model were used to analyze the related factors of prognosis. long-rank test was used to compare the difference of observation endpoint. P \< 0.05 was statistically significant.
Screening period: Subjects will complete screening evaluation within 28 days before the first medication to determine whether they meet the research conditions. During the screening period, the peripheral blood of the subjects should be collected.
Treatment period: The subjects who met the conditions of the study population were treated with Cadonilimab 10mg/kg + bevacizumab 7.5 mg/kg + carboplatin (AUC 5) + pemetrexed 500mg/m2. Every 3 weeks is a cycle, with a total of 4-6 cycles (the number of chemotherapy cycles is determined by the researchers). Cadonilimab 10mg/kg, bevacizumab 7.5 mg/kg and pemetrexed 500mg/m2 were then maintained until disease progression, intolerable toxicity or other causes specified in the regimen occurred. When the subject first has imaging disease progression, if the researcher judges that it is clinically beneficial and tolerant to the test drug, he will be allowed to continue treatment.
During the treatment, the researchers evaluated the curative effect according to RECIST 1.1 standard. ORR evaluated by researchers was used as the main curative effect index. Subjects were evaluated for tumor every 6 weeks (7 days) within 54 weeks after enrollment, and every 12 weeks (7 days) after enrollment. Subjects who stop taking drugs for non-disease progression reasons will continue to follow up their disease status until the subjects start other anti-tumor treatment, disease progression, withdrawal of consent, death or end of study, whichever occurs first.
During the treatment, researchers will collect a series of blood samples for pharmacokinetics, immunogenicity and exploratory research and analysis.
Adverse events (AE) of each subject will be collected until 30 days after the last administration or new anti-tumor treatment will be started, whichever occurs first. Serious adverse events (SAE) will be collected until 90 days after the last administration or new anti-tumor treatment will be started, whichever occurs first. Immune-related AE (irAE) will be collected until 90 days after the last administration or new anti-tumor therapy will be started, whichever occurs first. Survival assessment was performed every 3 months after the last dose to obtain survival information and collect information on subsequent anti-tumor treatment after termination of study treatment.
