HS-20093 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. 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 solid tumor patients.
This is a phase 1, open-label, multi-center, dose-escalation and expansion, phase 1 study in Chinses subjects with advanced solid tumors. 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 5 combination-treatments will be carried out in 3 cohorts. The target population of dose escalation part is 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. 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
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
610
administered as an IV infusion
administered as an IV infusion
administered as an IV infusion
Shanghai Chest Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGMaximum 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 solid tumors
Time frame: Up to day 21 from the first dose
Incidence and severity of adverse events (AEs)
AE assessed by investigator exclusively related to subject's underlying disease or medical condition \[graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0\]. Any untoward medical occurrence in a clinical study participant, whether or not considered related to the medicinal product. Incidence and severity of AEs are assessed according to vital signs, laboratory variables, physical examination, electrocardiogram, etc.
Time frame: From the first dose through 90 days post end of treatment
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). For prostate cancer patients, ORR is determined by investigators according to RECIST 1.1 and Prostate Cancer Working Group 3 (PCWG3).
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) \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks); SD shall be assessed at least 5 weeks after the first dose\]. For prostate cancer patients, DCR is determined by investigators according to RECIST 1.1 and Prostate Cancer Working Group 3 (PCWG3).
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administered as an IV infusion
160mg once daily (QD) orally
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 \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\]. For prostate cancer patients, DoR is determined by investigators according to RECIST 1.1 and Prostate Cancer Working Group 3 (PCWG3).
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.
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, whichever came first, assessed up to 24 months
Radiographic progression-free survival (rPFS) determined by investigators according to RECIST 1.1 and PCWG3
For prostate cancer patients, the rPFS is defined as the time from random assignment or first dose to the date of first documented PD per PCWG3 or death from any cause, whichever occurs first.
Time frame: From the first dose up to PD or death from study, whichever came first, assessed up to 24 months
Time to PSA progression (TTPP)
In participants with a decrease in PSA from baseline: ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir value, which is confirmed by a consecutive second value obtained ≥ 3 weeks later. In participants with no decrease in PSA from baseline: ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline value after 12 weeks.
Time frame: From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months
Prostate-specific cancer antigen (PSA) response rate
PSA response is defined as a ≥ 50% decline in PSA from baseline with PSA confirmation ≥ 3 weeks after the first documented reduction in PSA of ≥ 50%.
Time frame: From the first dose up to PD or withdrawal from study, whichever came first, assessed up to 24 months
Time to first subsequent therapy (TFST)
TFST was defined as the time from random assignment or first dose to the imitation of subsequent therapy or death.
Time frame: From the first dose up to the imitation of subsequent therapy or death, whichever came first, assessed up to 24 months
Observed maximum plasma concentration (Cmax) of HS-20093advanced solid tumor
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
T1/2 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
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