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. This is a phase 2, open-label, multi-center study to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of HS-20093 as a monotherapy in patients with relapsed or refractory osteosarcoma and other sarcomas.
This is a phase 2, open-label, multi-center study consisting of two parts: Phase 2a and 2b. Phase 2a: The study will be conducted in the following two cohorts: Cohort 1: Patients with advanced osteosarcoma upon disease progression after standard treatment. Cohort 2: Patients with other unresectable bone and soft tissue sarcomas, if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. Subjects will be randomly assigned in a 1:1 ratio to 8.0 mg/kg and 12.0 mg/kg of HS-20093 in cohort 1 and will receive 12.0 mg/kg in cohort 2. Phase 2b: The study will be conducted in patients with advanced osteosarcoma upon disease progression after standard treatment. Subjects will receive HS-20093 at the recommended dose from Phase 2a. All patients will be carefully followed for adverse events during the study treatment and for 90 days after the last dose of HS-20093. 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
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
170
IV administration of HS-20093 Q3W; Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.
Peking University People's Hospital
Beijing, China
RECRUITINGHunan Cancer Hospital
Changsha, China
RECRUITINGObjective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigators based on RECIST version 1.1\[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\].
Time frame: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
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.
Observed maximum plasma concentration (Cmax) of HS-20093
Cmax will be obtained following administration of the first dose of HS-20093 during the first cycle.
Time frame: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)
Time to reach maximum plasma concentration (Tmax) of HS-20093 following the first dose
Tmax will be obtained following administration of the first dose of HS-20093 during the first cycle.
Time frame: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)
Terminal half-life (T1/2) of HS-20093 following the first dose
Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
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First Affiliated Hospital, Sun Yat-Sen University
Guangzhou, China
Sun Yat-sen University Cancer Center
Guangzhou, China
RECRUITINGSecond Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, China
RECRUITINGZhejiang Cancer Hospital
Hangzhou, China
RECRUITINGChinese PLA General Hospital of Eastern Theater Command
Nanjing, China
RECRUITINGShanghai 6th People's Hospital
Shanghai, China
RECRUITINGShanghai General Hospital
Shanghai, China
RECRUITINGTianjin Cancer Hospital
Tianjin, China
RECRUITING...and 1 more locations
Time frame: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)
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 14 days after the first dose on Cycle 1 (each cycle is 21 days)
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 90 days post end of treatment
ORR determined by Independent review committee (IRC) according to RECIST 1.1
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by IRC based on RECIST version 1.1\[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\].
Time frame: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Duration of response (DoR) determined by investigators and IRC according to RECIST 1.1
DoR was 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: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Disease control rate (DCR) determined by investigators and IRC according to RECIST 1.1.
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: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Progression-free survival (PFS) determined by investigators and IRC according to RECIST 1.1
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). PFS was defined as the time from first dose or random assignment (if any) to PD or death from any cause.
Time frame: From the first dose or random assignment up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
4-month PFS rate determined by investigators and IRC according to RECIST 1.1
4-month PFS rate is defined as the percentage of patients whose disease is progression free at 4 months from the start of treatment.
Time frame: 4 months.
Overall survival (OS)
OS was defined as the time from the first dose or random assignment (if any) to death from any cause.
Time frame: From the first dose or random assignment up to death or withdrawal from study, whichever came first, assessed up to 24 months.