A Study Evaluating the Safety, Tolerability, and Initial Efficacy of IBI110 in Subjects With Advanced Malignant Tumors

Study Overview
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Brief Summary
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This is an open-label, dose escalation, Phase I study to evaluate the safety, tolerability, pharmacokinetics and efficacy of IBI110 in subjects with advanced malignancies.

Official Title
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A Phase 1a, Open-label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Initial Efficacy of IBI110 in Subjects With Advanced Malignant Tumors

Conditions
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Advanced Malignancies

Intervention / Treatment
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* Drug: IBI110
* Drug: IBI110
* Drug: IBI110+ Sintilimab
* Drug: IBI110+ Sintilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and willing to sign the ICF. Adults 18 years of age or older. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy at least 12 weeks. Adequate organ and bone marrow function. Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors and lymphomas that are refractory to standard therapy, or for which no standard therapy exists. Measurable disease according to RECIST Version 1.1 in solid tumor. Subjects (women of child-bearing potential and males) must be willing to use viable contraception method that is deemed effective by the investigator throughout the treatment period and for at least three months following the last dose of study drug. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Exclusion Criteria: Previous exposure to any anti-lag-3 antibody. Participate in another interventional clinical study, except for the observational (non-interventional) clinical study or the survival follow-up phase of the interventional study. Any investigational drugs received within 4 weeks prior to the first study treatment. Receive the last dose of anti-tumor therapy within 4 weeks before the first dose of study therapy. Immunosuppressive drugs were used within 4 weeks prior to the first administration of the study drug. Medication requiring long-term systemic hormones or any other immunosuppression therapy. Major surgical procedures (craniotomy, thoracotomy, or laparotomy) or unhealed wounds, ulcers, or fractures were performed within 4 weeks prior to the first dose of study therapy. There were unrecovered toxicity (excluding hair loss or fatigue) according to NCI CTCAE v5.0 induced by previous antitumor therapy (24 weeks before the first dose of study), and there were unrecovered immune-related adverse events (irAE) associated with immunotherapy. Previous immunotherapy, such as anti-PD-1 / anti-PD-L1 antibody or anti-CTLA4 antibody, was discontinued due to the presence of > grade 3 irAE. Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases, or leptomeningeal disease. History of autoimmune disease , present active autoimmune disease or inflammatory diseases Present or history of pulmonary diseases such as interstitial pneumonia, pneumoconiosis, drug-related pneumonia, pulmonary fibrosis, active pulmonary infection, severely impaired pulmonary function. Positive human immunodeficiency virus (HIV) test. Active hepatitis B or C, or tuberculosis. History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. 16. History of gastrointestinal perforation and/or fistula at 6 months prior to study inclusion. 17.Hydrothorax, ascites, and pericardial effusion with clinical symptoms requiring drainage. 18.Known history of hypersensitivity to any components of the IBI110 or Sintilimab. 19.Uncontrolled complications of disease. 20.Other acute or chronic illness, mental illness, or abnormal laboratory test values that may increase the risk of study participation or administration of study drugs, or interfere with the interpretation of study results. 21.History of other primary malignancies. 22. Pregnant or nursing females.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase Ia Dose-Escalation Stage:IBI110<br>Participants will be treated with escalating doses of IBI110 to determine the MTD. | Drug: IBI110<br>* Several dose levels will be evaluated for IBI110 administered as a single agent and in combination with Sintilimab. IBI110 will be given via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent IBI110 may receive combination treatment with IBI110 plus Sintilimab. Combination treatment may continue until disease progression or loss of clinical benefit.<br>|
| Experimental: Phase Ia Expansion Stage:IBI110<br>Participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of IBI110 in different cancer types. | Drug: IBI110<br>* IBI110 will be given with RP2D. IBI110 will be given via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or loss of clinical benefit.<br>|
| Experimental: Phase Ib Dose-Escalation Stage:IBI110+ Sintilimab<br>Participants will be treated with escalating doses of IBI110 in combination with a fixed dose of Sintilimab to determine the MTD. | Drug: IBI110+ Sintilimab<br>* IBI110: Several dose levels will be evaluated for IBI110 in combination with Sintilimab. IBI110 will be given via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or loss of clinical benefit. Sintilimab: Sintilimab will be given as 200 mg via IV infusion on Day 1 of each 21-day cycle in combination with IBI110. Combination treatment may continue until disease progression or loss of clinical benefit.<br>|
| Experimental: Phase Ib Expansion Stage:IBI110+ Sintilimab<br>Participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of IBI110 in combination with Sintilimab in different cancer types. | Drug: IBI110+ Sintilimab<br>* IBI110: IBI110 in combination with Sintilimab will be given with RP2D. IBI110 will be given via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or loss of clinical benefit. Sintilimab: Sintilimab will be given as 200 mg via IV infusion on Day 1 of each 21-day cycle in combination with IBI110. Combination treatment may continue until disease progression or loss of clinical benefit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with AEs and SAEs | To evaluate the safety and tolerability of IBI110 alone or in combination with Sintilimab [Adverse events (AEs), Serious Adverse Events (SAEs) ] | up to 2 years after enrollment | 
| Percentage of Participants with Dose-Limiting Toxicities (DLTs) | To evaluate the safety and tolerability of IBI110 alone or in combination with Sintilimab. | From Baseline to the end of Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: AUC | The area under the curve (AUC) of serum concentration of the drug after the administration. | up to 2 years after enrollment | 
| Pharmacokinetics: Cmax | Maximum concentration (Cmax) of the drug after administration | up to 2 years after enrollment | 
| Immunogenicity: Percentage of ADA positive subjects | Immunogenicity: Number of Anti-Drug Antibodies (ADA) positive subjects will be counted and percentage of ADA positive subjects will be calculated to evaluate immunogenicity of IBI110. | up to 2 years after enrollment | 
| Preliminary anti-tumor activity of IBI110 (Objective Response Rate) | Objective Response Rate (ORR) is the percentage of Complete Response (CR) plus partial response (PR) assessed by RECIST v1.1 criteria for solid tumors and Lugano2014 criteria for lymphoma. | up to 2 years after enrollment |