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. HRS-5041 is a Proteolysis Targeting Chimeras (PROTAC) targeting androgen receptors. This is a phase Ib, open-label, multi-center study to evaluate the safety, tolerability, and pharmacokinetics (PK) of HS-20093 combination with HRS-5041 in patients with advanced prostate cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Fudan University Shanghai Cancer Center
Shanghai, China
RECRUITINGTo determine the maximum tolerated dose (MTD) or Maximum Administrated dose (MAD)
Number of participants with dose limiting toxicity
Time frame: 21 days from administration of the first dose (C1D1) in the dose escalation phase， assessed up to 24 months
To evaluate the 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 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(C1D1) up to 30 days after the last dose of HRS-5041 or 90 days after the last dose of HS-20093 (whichever is later)
To evaluate the maximum plasma concentration (Cmax)
Cmax will be obtained following administration of the first dose of HS-20093 during the first cycle
Time frame: up to approximately 24 months
To evaluate the Time to reach maximum plasma concentration (Tmax)
Tmax will be obtained following administration of the first dose of HS-20093 during the first cycle
Time frame: up to approximately 24 months
To evaluate the Area under plasma concentration versus time curve from zero to last sampling time (AUC)
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: up to approximately 24 months
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To evaluate the immunogenicity of HS-20093
Proportion of patients who are positive for anti-HS-20093 antibodies
Time frame: up to approximately 24 months
To evaluate the ORR determined by investigators
Objective response rate (ORR) determined by IRC according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Prostate Cancer Working Group 3 (PCWG3)
Time frame: up to approximately 24 months
To evaluate the Disease control rate (DCR) determined by investigators according to RECIST 1.1 and PCWG3
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). 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: up to approximately 24 months
To evaluate the Duration of response (DoR) determined by investigators according to RECIST 1.1 and PCWG3
DoR is defined as the period from the first occurrence of CR or PR to progressive disease (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: up to approximately 24 months
To evaluate the Prostate-specific Cancer Antigen (PSA) response rate（PSA30,PSA50,PSA90）
PSA response is defined as a ≥ 30%，≥ 50% ，≥ 90% decline in PSA from baseline with PSA confirmation ≥ 3 weeks after the first documented reduction
Time frame: up to approximately 24 months
To evaluate the Time to PSA progression
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: up to approximately 24 months