This study is a phase Ia study of single drug BR101 for Advanced solid tumor. The main purpose of this study is to Evaluate the safety and tolerability of BR101monotherapy (single dose and multiple doses) in Subjects with Advanced Solid Tumors and determine the MTD if possible, and determine the RP2D. The secondary purpose of this study is to explore the Pharmacokinetics, Immunogenicity, Antitumor Activity of BR101 monotherapy (single dose and multiple doses) in Subjects with Advanced Solid Tumors
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
BR101 injection was administered once for 28 days observation period and then weekly until the subject experienced unacceptable toxicity, disease progression, poor compliance, pregnancy, informed withdrawal, death, study interruption, and withdrawal from the study
The Second Affiliated Hospital of Zhejiang University Medical College
Hangzhou, Zhejiang, China
Safety, Tolerability,RP2D
The incidence and severity of various adverse events of DLT, evaluated per NCI CTCAE 5.0 standard, abnormal physical examination, vital signs, laboratory examination, 12-guided ECG, etc.; maximum tolerated dose (MTD)(if possible). Recommended Phase II clinical trial dose
Time frame: up to 91 days after the last administration
Cmax
Cmax
Time frame: From screening to 31 days after the last administration
Tmax
Tmax
Time frame: From screening to 31 days after the last administration
AUC0-last
AUC0-last
Time frame: From screening to 31 days after the last administration
AUC0-tau
AUC0-tau
Time frame: From screening to 31 days after the last administration
Cmin
Cmin
Time frame: From screening to 31 days after the last administration
Immunogenicity assessment
Anti-drug antibody (ADA) level produced by subjects
Time frame: From screening to 31 days after the last administration
DCR
DCR
Time frame: up to end of day 71
DoR
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DoR
Time frame: up to end of day 71
TTR
TTR
Time frame: up to end of day 71
CR
CR
Time frame: up to end of day 71
PFS
PFS
Time frame: up to end of day 71
Objective response rate(ORR)
ORR
Time frame: up to end of day 71
Pharmacodynamic assessment
After administration, to evaluate Total/free CD73 level in peripheral blood, CD73 enzymatic activity in peripheral blood, CD73 level and CD73 occupancy of peripheral blood T lymphocytes, CD73 level and CD73 occupancy of tumor tissue, CD73 enzymatic activity in tumor tissue, CD8+ tumor infiltrating lymphocyte level in tumor tissue.
Time frame: UP to end of day 102