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 head and neck squamous cell carcinoma and other solid tumors.
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 recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) who have progressed on or intolerant to standard therapies. Cohort 2: Other patients with advanced solid tumors if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. All subjects will receive 10.0 mg/kg of HS-20093. Phase 2b: The study will be conducted in patients with recurrent/metastatic HNSCC who have progressed on or intolerant to standard therapies. Subjects will receive 10.0 mg/kg of HS-20093. 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
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
170
Participants in all subjucts will receive HS-20093 at 10mg/kg
Objective 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, which ever 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 in participants with advanced solid tumor
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 IV dose in participants with advanced solid tumor
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Anhui Cancer Hospital
Hefei, Anhui, China
RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGBeijing Tongren Hospital, CMU
Beijing, Beijing Municipality, China
RECRUITINGFujian Cancer Hospital
Fuzhou, Fujian, China
RECRUITINGSun Yai-Sen Memorial Hospital Sun Yai-Sen University
Guangzhou, Guangdong, China
RECRUITINGSun Yat-Sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGThe Fifth Affiliated Hospital Sun Yat-Sen University
Zhuhai, Guangdong, China
RECRUITINGGuangxi Medical University Cancer Hospital
Nanning, Guangxi, China
RECRUITINGHarbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITING...and 15 more locations
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
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
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