Non-small Cell Lung Cancer (NSCLC)
Conditions
Brief summary
The main purpose of this study is to evaluate the neoadjuvant therapy efficacy of IBI110 in combination with sintilimab versus sintilimab alone based on pathologic complete response (pCR) rate in stage IIB (primary tumor \> 4 cm ) to IIIB (N2 only) subjects with radically resectable NSCLC.
Interventions
DRUGIBI110
R2PD d1 IV every 3 weeks
DRUGsintilimab
200mg d1 IV every 3 weeks
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have NSCLC that has been classified as stage IIB (primary tumor \> 4 cm), IIIA, or IIIB (N2 only) per the 8th edition of TNM staging system of International Association for the Study of Lung Cancer (IASLC) and the American Joint Committee on Cancer (AJCC). 2. Subjects with non-squamous NSCLC should undergo genetic testing to confirm the absence of epidermal growth factor receptor (EGFR) sensitizing mutations or anaplastic lymphoma kinase (ALK) rearrangements; 3. Eligible for radical resection (R0 resection) at the thoracic surgeon's discretion, and the lung function meets the criteria for planned surgery; 4. Have at least one measurable lesion per RECIST v1.1 criteria; 5. Have a performance scale of 0 or 1 on the Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Exclusion criteria
1. Have pathological evidence for small cell carcinoma, neuroendocrine carcinoma, sarcoma, lymphoepithelial rumen carcinoma, salivary gland tumor, or mesenchymal tumor from the biopsy. 2. Have been previously exposed to immune-mediated therapies, including but not limited to LAG-3 antibody drugs, anti-cytotoxic T lymphocyte antigen-4 (CTLA-4), anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pCR | Approximately 21 to 28 days after operation | defined as having no residual visible tumor cells in the surgically resected primary tumor and lymph node samples (ypT0N0) |
| Incidence of serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs) | up to 90 days after the last administration | An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. A TEAE will be defined as any new AE that begins, or any pre-existing condition that worsens in severity, after at least 1 dose of study treatment has been administered. irAEs will be assessed. |
| Number of participants with abnormality in vital signs | up to 90 days after the last administration | Blood pressure, pulse, respiratory rate, and temperature will be assessed. |
| Number of participants with abnormality in hematology parameters | up to 90 days after the last administration | Blood samples will be collected to evaluate hemoglobin, mean corpuscular volume (MCV), white blood cell (WBC) count, platelets, 5-part differential white cell count, mean platelet volume and coagulation factors including international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT). |
| Number of participants with abnormality in clinical chemistry parameters | up to 90 days after the last administration | Blood samples will be collected to evaluate sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or blood urea nitrogen (BUN), bicarbonate, amylase, bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, lactate dehydrogenase and lipase. |
| Number of participants with abnormality in routine urinalysis parameters | up to 90 days after the last administration | Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, bilirubin, protein, glucose, ketones and urobilinogen. |
| Number of participants with abnormality in ECG parameters | up to 90 days after the last administration | 12-lead ECG will be obtained using an ECG machine. Participants will be in supine or a semi-recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs are recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the area under the drug plasma concentration-time curve (AUC) | from first administration of IBI110 to 3 days before the operation | Area under the concentration-time curve from time zero to last measurable concentration (AUC) |
| half-life (t1/2) | from first administration of IBI110 to 3 days before the operation | defined as the time it takes for the concentration of IBI110 and Sintilimab in the plasma or the total amount in the body to be reduced by 50%. |
| EFS （Event Free Survival） | up to 3 years | defined as time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, or death due to any cause |
| volume of distribution (V). | from first administration of IBI110 to 3 days before the operation | calculated by the amount of the drug in the body divided by the plasma concentration. |
| clearance (CL) | from first administration of IBI110 to 3 days before the operation | a pharmacokinetic measurement of the volume of plasma from which IBI110 and Sintilimab are completely removed per unit time |
| major pathological response (MPR) rate | Approximately 21 to 28 days after operation | defined as ≤ 10% residual viable tumor cells in the surgically resected primary tumor and lymph nodes |
| radical resection (R0 resection) rate | Approximately 21 to 28 days after operation | defined as free resection margins, systematic node dissection or sampling, and the highest mediastinal node negative for tumor |
| ORR （Objective Response rate,） | Within 7 days before surgery | defined as the ratio of subjects who have achieved investigator assessed complete response (CR) and partial response (PR) per RECIST v1.1 |
| OS （Overall Survival） | up to 3 years | defined as the time from randomization to death from any cause |
| Immunogenicity | From date of randomization to 30 days after last dose of the drug | includes the positive rate of anti-drug antibody (ADA) and neutralizing antibody (NAb) in subjects |
| maximum concentrations (Cmax ) | from first administration of IBI110 to 3 days before the operation | Maximum serum concentration that IBI110 and Sintilimab achieves in the body after the drug has been administered and before the administration of a second dose. |
Countries
China
Outcome results
None listed