First in Human Study of IBI101 in Chinese Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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Phase 1a/1b Trial to evaluate the tolerability and safety of IBI101 monotherapy or in combination with Sintilimab in advanced solid tumor patients.

Detailed Description
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IBI101 and Sintilimab will be administered intravenously on Day 1 of every 21-day cycle. The DLT observation period is 21 days starting with the first dose taken on day 1. In the Phase Ia study, eight dose levels of IBI101 (0.01, 0.1, 0.3, 1, 3, 6, 10 and 15mg/kg) will be tested. In the Phase Ib study, four dose levels of IBI101 (1, 3, 6 and 10mg/kg), in combination with Sintilimab 200mg, will be tested. After completion of the dose escalation phase, two combination dose cohorts (IBI101 3mg/kg and 6mg/kg, in combination with Sintilimab 200mg) will be expanded to 10 patients each. IBI101 is a recombinant fully humanized IgG1 anti-tumor necrosis factor receptor superfamily member 4 (OX40) monoclonal antibody. Sintilimab is a recombinant fully humanized anti-programmed death 1 (PD1) monoclonal antibody.

Official Title
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Phase Ia/Ib Trial to Evaluate the Tolerability and Safety of IBI101 Monotherapy or in Combination With Sintilimab in Advanced Solid Tumor Patients

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: IBI101
* Drug: IBI101
* Drug: Sintilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with locally advanced, recurrent or metastatic solid tumors who have failed standard treatment 18 to 75 years old Life expectancy ≥ 12 weeks At least 1 measurable lesion ECOG PS score 0 or 1 Adequate organ and bone marrow function Exclusion Criteria: Previous exposure to anti-OX40, anti-PD-1, anti-PD-L1, anti-PD-L2 antibody or other immune checkpoint inhibitors Exposure to any other investigational drug in the 4 weeks prior to 1st dose of investigational drug Exposure to anti-tumor agents in the 3 weeks prior to 1st dose of investigational drug Exposure to immunosuppressant in the 3 weeks prior to 1st dose of investigational drug Major surgery in the 4 weeks prior to 1st dose of investigational drug 30Gy radiation in the chest in the 6 months prior to 1st dose of investigational drug History of autoimmune disease Symptomatic CNS metastasis

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI101<br>IBI101 will be administrated intravenously. 3+3 dose escalation design will be used with eight dose levels being tested. | Drug: IBI101<br>* 0.01 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 6 mg/kg; 10 mg/kg; 15 mg/kg iv infusion day 1 of every 21 days<br>|
| Experimental: IBI101 in combination with Sintilimab<br>IBI101 and Sintilimab will be administrated intravenously. 3+3 dose escalation design will be used with 4 dose levels of IBI101 being tested. Two dose levels of IBI101 in combination with Sintilimab will be expanded to 10 patients each. | Drug: IBI101<br>* 1 mg/kg; 3 mg/kg; 6 mg/kg; 10 mg/kg iv infusion day 1 of every 21 days<br>Drug: Sintilimab<br>* 200mg iv infusion day 1 of every 21 days<br>* Other names: IBI308;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incicende of Adverse Events (AEs) | Number of patients with AE, treatment-related AE (TRAE), immune-related AEs (irAE), AE of special interest (AESI), serious adverse event (SAE), discontinuation of study drug due to AE, dose-limiting toxicity (DLT) assessed by CTCAE v5.0. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) |  | 2 years | 
| Time to response (TTR) |  | 2 years | 
| Duration of response (DOR) |  | 2 years | 
| Progression free survival (PFS) |  | 2 years | 
| Area Under Curve (AUC)last and AUC0-inf |  | 2 years | 
| Maximum Concentration (Cmax) |  | 2 years | 
| Total body clearance (CL) |  | 2 years | 
| Volume of distribution (Vz) |  | 2 years | 
| Time at which maximum concentration occurred (Tmax) |  | 2 years | 
| Elimination half-life (t1/2) |  | 2 years | 
| Mean residue time (MRT) |  | 2 years | 
| OX40 receptor occupancy |  | 2 years | 
| T cell subset analysis |  | 2 years | 
| Anti-drug antibody (ADA) |  | 2 years | 
| Neutralizing antibody (Nab) positive rate |  | 2 years |