Advanced NSCLC
Conditions
Keywords
Tumor Neoantigen, Peptide Vaccine, NSCLC, Immunotherapy, PD-1 Inhibitor, Radiotherapy
Brief summary
In this study, the investigators provide a combined treatment of personalized tumor neoantigen-based peptide vaccine, PD-1 Inhibitor, and radiotherapy to patients with advanced non-small cell lung cancer (NSCLC) progressed after first-line treatment. The investigators observe the objective response rate (ORR), disease control rate (DCR), adverse event (AE), serious adverse event (SAE), progression-free survival (PFS), and overall survival (OS) , aiming to evaluate the effectiveness and safety of the treatment.
Detailed description
This study is conducted in accordance with the Declaration of Helsinki and the guidelines of the Consolidated Standards of Reporting Trials. 10 patients with advanced NSCLC progressed after first-line treatment will be recruited in this study. With doctor's assessment, a combined treatment of PD-1 inhibitor, radiotherapy, and personalized tumor neoantigen-based peptide vaccine treatment plan will be designed for each participant. Here are the steps for preparing the neoantigen-based peptide vaccine: Collecting venous blood samples; Blood PBMC exome sequencing; RNA transcriptome sequencing; Classifying HLA alleles; Performing bioinformatics analysis, finding meaningful mutations and about 20 neoantigen sequences for each patient; Synthesizing peptide neoantigens; Preparation of the personalized tumor neoantigen-based peptide vaccine. Participants will receive a personalized radiotherapy treatment course, followed with PD-1 inihibitor injections (every 3 weeks) and 10 subcutaneous injections of the vaccine within a treatment period of 21 weeks. After treatment, participants will be followed in every 6 weeks till the end of the study. Venous blood collection, physical examination, ECOG Performance Status Scale assessment, CT/MRI scan, X-ray examination, laboratory examination, and other necessary examinations are required at each follow-up visit.
Interventions
RADIATIONRadiotherapy
Radiotherapy will be completed prior to the administration of personalized tumor neoantigen-based peptide vaccine and PD-1 inhibitors. The treatment cycle, frequency, and dosage are determined by the subject's primary physician based on the specific conditions of the participant.
DRUGPD-1 inhibitor
Treatment with PD-1 inhibitors will begin after the completion of radiotherapy, with a treatment cycle of 3 weeks. On the first day (D1) of each treatment cycle, the drug is administered intravenously, with the dosage according to the instructions.
The treatment with personalized tumor neoantigen-based peptide vaccine is divided into two periods: the primary phase and the boost phase. The primary phase consists of 6 treatments, with the first 3 treatments spaced one week apart and the subsequent 3 treatments spaced two weeks apart. Vaccine will be administrated on the fourth day (D4) of that week. The boost phase consists of 4 treatments, each spaced three weeks apart. Vaccine will be administrated on the fourth day (D4) of that week.
Sponsors
The First Affiliated Hospital of Nanchang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with histologically or cytologically confirmed advanced NSCLC who require radiotherapy for metastatic lesions; * At least one measurable lesion; * Aged 18-70, regardless of gender; * Disease progression after standard first-line therapy, and more than 2 weeks since the end of the last antitumor treatment; * Expected survival of ≥3 months; * ECOG performance status of 0-1; * Female patients of childbearing age must have a negative pregnancy test and be able to take effective contraceptive measures with no plans for pregnancy within six months of the study; * Able to undergo all screening period laboratory tests as required by the protocol; * Normal major organ function, such as heart, liver, and kidney; * Hematologic parameters: neutrophil count ≥1.5×10\^9/L, hemoglobin ≥10g/dL, platelet count ≥100×10\^9/L, total bilirubin ≤1.5 times the upper limit of normal, AST and ALT ≤2.5 times the upper limit of normal, creatinine and blood urea nitrogen ≤1.5 times the upper limit of normal, activated partial thromboplastin time ≤1.5×ULN, and International Normalized Ratio or prothrombin time ≤1.5×ULN; * No active hepatitis, AIDS, syphilis, or other infectious diseases; * Rheumatoid panel: C-reactive protein (CRP) ≤10.0mg/L; Anti-streptolysin O (ASO) \<500U; Erythrocyte sedimentation rate ≤15mm/h (men) or 20mm/h (women); * Thyroid function tests: 0.27mIU/L ≤ Thyroid-stimulating hormone (TSH) ≤ 4.2mIU/L; 3.1pmol/L ≤ Free triiodothyronine (FT3) ≤ 6.8pmol/L; 12pmol/L ≤ Serum free thyroxine (FT4) ≤ 22pmol/L; 1.3nmol/L ≤ Serum total triiodothyronine (TT3) ≤ 3.1nmol/L; 66nmol/L ≤ Serum total thyroxine (TT4) ≤ 181nmol/L; * Adrenocorticotropic hormone (ACTH): 1.1-17.6pmol/L; * Ability to understand and voluntarily sign a written informed consent form.
Exclusion criteria
Disease-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Through study completion, an average of 30 weeks | According to RECIST (version 1.1) criteria, the proportion of subjects experiencing Complete Response (CR) or Partial Response (PR) within the analyzed population. Provide the 95% CI for the Objective Response Rate (ORR). |
| Disease control rate (DCR) | Through study completion, an average of 30 weeks | According to RECIST (version 1.1) criteria, the proportion of subjects experiencing Complete Response (CR), Partial Response (PR), or Stable Disease (SD) within the analyzed population. Provide the 95% CI for the Disease Control Rate (DCR). |
| Drug safety | Through study completion, an average of 30 weeks | Safety analysis will be based on data from the safety population. It will primarily involve descriptive statistical analysis, with tables describing the adverse events that occurred in this study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From date of recruiting until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 66 months | Progression-Free Survival (PFS) is defined as the time from the first administration of the study drug to disease progression or death. For subjects who have not reported disease progression at the time of analysis, the date of their last disease progression-free check will be used as the censoring date. The median PFS and its 95% CI will be analyzed using the Kaplan-Meier method, and survival curves will be plotted. |
| Overall Survival (OS) | From date of recruiting until the date of death from any cause, whichever came first, assessed up to 66 months | Overall Survival (OS) is defined as the time from the first administration of the study drug to death from any cause. For subjects who have not reported death at the time of analysis, the date of their last known survival will be used as the censoring date. The median OS and its 95% CI will be analyzed using the Kaplan-Meier method, and survival curves will be plotted. |
Countries
China
Contacts
Primary ContactYong Li, MD
Outcome results
None listed