This is a Phase 1, global, multi-center, open-label, multiple-dose, first-in-human study of MIL97 to evaluate the safety, tolerability, pharmacokinetics, biomarkers and efficacy in subjects with advanced or metastatic solid tumor. The study consists of a dose escalation phase and a dose expansion phase. An accelerated titration design (cohorts 1-2 only) followed by 3+3 dose-escalation design will be used in dose escalation phase. The starting dose for dose escalation phase is 0.01 mg/kg Q3W, followed by 5 dose cohorts (0.03mg/kg Q3W, 0.1mg/kg Q3W, 0.2mg/kg Q3W, 0.3mg/kg Q3W and 0.45mg/kg Q3W). Duration of dose limiting toxicity (DLT) observation is 21 days. Based on data of 3-week treatment regimen, one or two dose levels may be chosen for Q2w regimen. Duration of dose limiting toxicity (DLT) observation is 28 days. One or two dose cohorts will be chosen (either 2-week regimen or 3-week regimen cohorts) to expand to total of 10 subjects in each cohort for further exploration of PK as well as safety and efficacy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
62
Dose escalation phase: The patients confirming to the eligibility criteria will be assigned to the 6 dose groups (0.01mg/kg, 0.03mg/kg, 0.1mg/kg, 0.2mg/kg, 0.3mg/kg 0.45mg/kg, respectively) based on the sequence of inclusion. Each patient will receive an intravenous infusion of MIL97 every 3 week on Day 1 of each cycle. Additional 1 or 2 dose cohorts will receive an intravenous infusion of MIL97 every 2 week on Day 1 of each cycle after last patient finishes DLT observation period. Dose expansion phase: One or two recommended expansion doses (either Q3W or Q2W) will be selected from 6 dose groups (0.01mg/kg, 0.03mg/kg, 0.1mg/kg, 0.2mg/kg, 0.3mg/kg 0.45mg/kg) based on results of dose escalation phase. MIL97 will be administered via intravenous infusion for 60 to 90 minutes on Day 1 of each cycle.
Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe incidence of MIL97 treatment-emergent adverse events in patients with advanced or metastatic solid tumor
incidence of AEs and SAEs assessed by NCI CTCAE v5.0.
Time frame: up to 2.5 year after enrollment
Pharmacokinetics: AUC
The area under the curve (AUC) of serum concentration of the drug after the administration
Time frame: up to 1.5 year after enrollment
Pharmacokinetics: Cmax;
Maximum concentration (Cmax) of the drug after administration
Time frame: up to 1.5 year after enrollment
Objective response rate (ORR);
To evaluate preliminary anti-tumor activity of MIL97 in subjects with advanced or metastatic solid tumor. ORR includes complete remission (CR) and partial remission (PR) assessed by RECIST v1.1 criteria.
Time frame: up to 2.5 year after enrollment
Duration of response (DoR);
DOR is defined as the time from the initial response (CR or PR) to the time of disease progression or death, whichever occurs first.
Time frame: up to 2.5 year after enrollment
Progression free survival (PFS);
Defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.
Time frame: up to 2.5 year after enrollment
The overall survival for patients with advanced or metastatic solid tumor;
Defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.
Time frame: up to 2.5 year after enrollment
The Disease control rate for patients with advanced or metastatic solid tumor;
Defined defined as the proportion of patients with objective evidence of CR, PR, or SD.
Time frame: up to 2.5 year after enrollment
Immunogenicity;
Anti-Drug Antibodies (ADA) will be tested and percentage of ADA positive patients will be calculated to evaluate immunogenicity of MIL97.
Time frame: up to 2.5 year after enrollment
Biomarkers;
measurement of CD80, CD86 and cytokines in human plasma
Time frame: up to 2.5 year after enrollment
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