HS-20093 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on bone and soft tissue sarcoma. The objectives of this study are to investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of HS-20093 in combination with other anti-cancer agents in patients with advanced bone and soft tissue sarcoma.
This is a phase 1b, open-label, multi-center, dose-escalation and expansion study in subjects with advanced bone and soft tissue sarcoma. This study is in design allowing assessment of safety, tolerability, pharmacokinetics and anti-tumor activity of HS-20093 in combination with other anti-cancer agents. A total of 4 combination-treatments will be carried out in 2 cohorts. The target population in cohort 1 of dose escalation part is soft tissue sarcoma patients have progressed on or intolerant to available standard therapies, and the dose expansion part will enroll patients who have not received prior treatment for advanced/metastatic disease. The target population in cohort 2 will enroll patients with osteosarcoma have progressed on or intolerant to available standard therapies All patients will be carefully followed for adverse events during the study treatment and for 90 days after the last dose of study drug. Subjects will be permitted to continue therapy with assessments for progression if the product is well tolerated and sustained clinical benefit exists
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
448
HS-20093: administered as an IV infusion
Anlotinib: 12mg once daily (QD) orally
Epirubicin: administered as an IV infusion
Maximum tolerated dose (MTD) for combination-treatments
To determine the MTD for further evaluation of HS-20093 with other anti-cancer agents in subjects with advanced bone and soft tissue sarcoma.
Time frame: Up to day 21 from the first dose
Objective response rate (ORR) determined by investigators
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline. ORR is evaluated by the number of participants with best overall response of CR and PR (Confirmed CR/PR assessment require at least 1 repeat).
Time frame: From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months
Disease control rate (DCR) determined by investigators
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline. DCR was evaluated by the number of participants with best overall response of CR, PR and stable disease (SD) \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks); SD shall be assessed at least 5 weeks after the first dose\].
Time frame: From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months
Duration of response (DoR) determined by investigators
DoR was defined as the period from the first occurrence of CR or PR to PD or death from any cause. If no PD or death after CR/PR, the cut-off date of progression-free survival (PFS) would be used \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\].
Time frame: From the first dose up to PD or death, whichever came first, assessed up to 24 months
Progression-free survival (PFS) determined by investigators according to RECIST 1.1
PFS was defined as the time from random assignment or first dose to PD or death from any cause
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Adebrelimab: administered as an IV infusion
Time frame: From the first dose up to PD or death, whichever came first, assessed up to 24 months
Overall survival (OS)
OS was defined as the time from random assignment or first dose to death from any cause.
Time frame: From the first dose up to death, assessed up to 24 months
Observed maximum plasma concentration (Cmax) of HS-20093
Cmax will be obtained after administration of the first dose of HS-20093
Time frame: From pre-dose to study completion, assessed up to 24 months
Time to reach maximum plasma concentration (Tmax) of HS-20093
Tmax will be obtained after administration of the first dose of HS-20093
Time frame: From pre-dose to study completion, assessed up to 24 months
Terminal half-life (T1/2) of HS-20093 following the first dose
T1/2will be obtained after administration of the first dose of HS-20093
Time frame: From pre-dose to study completion, assessed up to 24 months
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-20093
Area under the plasma concentration versus time curve from time zero to the last sampling time when the concentration was no less than the lower limit of quantification (LLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Time frame: From pre-dose to study completion, assessed up to 24 months
Percentage of participants with antibodies to HS-20093 in serum
Serum samples were collected for the determination of anti-drug antibody (ADA) at designated time points.
Time frame: From pre-dose to study completion, assessed up to 24 months