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

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: IBI110; Drug: sintilimab

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IBI110+sintilimab; IBI110 and sintilimab will be administered as intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks) for 3 cycles during the neoadjuvant treatment phase. IBI110 and sintilimab will be administered as IV infusion 3 weeks during the post-operative adjuvant phase up to 1 year.	Drug: IBI110; R2PD d1 IV every 3 weeks; Drug: sintilimab; 200mg d1 IV every 3 weeks
Active Comparator: sintilimab; Sintilimab will be administered as intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks) for 3 cycles during the neoadjuvant treatment phase. Sintilimab will be administered as IV infusion 3 weeks during the post-operative adjuvant phase up to 1 year.	Drug: sintilimab; 200mg d1 IV every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
OS （Overall Survival）	defined as the time from randomization to death from any cause	up to 3 years
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2021
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 25, 2023

Study Registration Dates

• First Submitted: September 28, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CIBI110C201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No