Efficacy and Safety of IBI110 in Combination With Sintilimab Versus Sintilimab Alone in Neoadjuvant and Adjuvant Therapy of Radically Resectable Non-small Cell Lung Cancer

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

Official title:

A Randomized, Open-label, Phase Ib Clinical Study to Evaluate the Efficacy and Safety of IBI110 in Combination With Sintilimab Versus Sintilimab Alone in Neoadjuvant and Adjuvant Therapy of Radically Resectable Non-small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05088967
• Other study ID #: CIBI110C201
• Status: Terminated
• Phase: Phase 1
• Start date: December 2, 2021
• Est. completion date: December 25, 2023

Study information

• Verified date: January 2024
• Source: Innovent Biologics (Suzhou) Co. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: December 25, 2023
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• IBI110
R2PD d1 IV every 3 weeks
• sintilimab
200mg d1 IV every 3 weeks

Locations

Country	Name	City	State
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Innovent Biologics (Suzhou) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pCR	defined as having no residual visible tumor cells in the surgically resected primary tumor and lymph node samples (ypT0N0)	Approximately 21 to 28 days after operation
Primary	Incidence of serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs)	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.	up to 90 days after the last administration
Primary	Number of participants with abnormality in vital signs	Blood pressure, pulse, respiratory rate, and temperature will be assessed.	up to 90 days after the last administration
Primary	Number of participants with abnormality in hematology parameters	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).	up to 90 days after the last administration
Primary	Number of participants with abnormality in clinical chemistry parameters	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.	up to 90 days after the last administration
Primary	Number of participants with abnormality in clinical chemistry parameters	Blood samples will be collected to evaluate sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or BUN, bicarbonate, amylase, bilirubin, alkaline phosphatase, AST, ALT, total protein, albumin, lactate dehydrogenase and lipase.	up to 90 days after the last administration
Primary	Number of participants with abnormality in routine urinalysis parameters	Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, bilirubin, protein, glucose, ketones and urobilinogen.	up to 90 days after the last administration
Primary	Number of participants with abnormality in ECG parameters	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.	up to 90 days after the last administration
Secondary	EFS (Event Free Survival)	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	up to 3 years
Secondary	major pathological response (MPR) rate	defined as = 10% residual viable tumor cells in the surgically resected primary tumor and lymph nodes	Approximately 21 to 28 days after operation
Secondary	radical resection (R0 resection) rate	defined as free resection margins, systematic node dissection or sampling, and the highest mediastinal node negative for tumor	Approximately 21 to 28 days after operation
Secondary	ORR (Objective Response rate,)	defined as the ratio of subjects who have achieved investigator assessed complete response (CR) and partial response (PR) per RECIST v1.1	Within 7 days before surgery
Secondary	OS (Overall Survival)	defined as the time from randomization to death from any cause	up to 3 years
Secondary	Immunogenicity	includes the positive rate of anti-drug antibody (ADA) and neutralizing antibody (NAb) in subjects	From date of randomization to 30 days after last dose of the drug
Secondary	maximum concentrations (Cmax )	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.	from first administration of IBI110 to 3 days before the operation
Secondary	the area under the drug plasma concentration-time curve (AUC)	Area under the concentration-time curve from time zero to last measurable concentration (AUC)	from first administration of IBI110 to 3 days before the operation
Secondary	half-life (t1/2)	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%.	from first administration of IBI110 to 3 days before the operation
Secondary	clearance (CL)	a pharmacokinetic measurement of the volume of plasma from which IBI110 and Sintilimab are completely removed per unit time	from first administration of IBI110 to 3 days before the operation
Secondary	volume of distribution (V).	calculated by the amount of the drug in the body divided by the plasma concentration.	from first administration of IBI110 to 3 days before the operation