Advanced Solid Tumor
Conditions
Brief summary
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
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.
Interventions
DRUGIBI101
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
DRUGSintilimab
200mg iv infusion day 1 of every 21 days
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incicende of Adverse Events (AEs) | 2 years | 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. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Duration of response (DOR) | 2 years |
| Overall response rate (ORR) | 2 years |
| Time to response (TTR) | 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 |
| Mean residue time (MRT) | 2 years |
Countries
China
Outcome results
None listed