HS-20089 is an investigational antibody-drug conjugate (ADC) composed of a humanized IgG1 anti-B7-H4 monoclonal antibody conjugated to the topoisomerase I inhibitor payload via a protease-cleavable linker, with an average drug-to-antibody ratio of about 6. This is a phase 2, open-label, multi-center study to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of HS-20089 as monotherapy in patients with recurrent or metastatic ovarian cancer and endometrial cancer.
This is a phase 2, open-label, multi-center study composed of two parts: phase 2a and phase 2b. Phase 2a: This part of study will be conducted in the following four cohorts: Cohort 1: Patients with platinum-resistant ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Cohort 2: Patients with recurrent or metastatic endometrial cancer who have progressed on or are intolerant to at least one line of standard platinum-based chemotherapy. Cohort 3: Patients with platinum-sensitive ovarian cancer, fallopian tube cancer or primary peritoneal cancer who have progressed on or are intolerant to at least two lines of standard platinum-based chemotherapy. Cohort 4: Patients with other advanced solid tumors who have progressed on or are intolerant to established standard therapies. Patients in cohort 1 will be randomly assigned 1:1 to receive HS-20089 at 4.8 mg/kg or 5.8 mg/kg and patients in the other three cohorts will receive HS-20089 at 5.8 mg/kg. Phase 2b: This part of study will be conducted in the following two cohorts: Cohort 1: Patients with platinum-resistant ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Cohort 2: Patients with recurrent or metastatic endometrial cancer who have progressed on or are intolerant to at least one line of standard platinum-based chemotherapy. The cohorts may be adjusted based on the observed clinical results, translational medicine data and research progress in the field. All patients will receive HS-20089 at the recommended dose (RD) determined by accumulated research data.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
460
All patients will receive intravenous HS-20089 once every three weeks (Q3W) until experiencing objective disease progression (except for study drug treatment beyond progression) or meeting other protocol-specified criteria of study treatment discontinuation.
Anhui Provincial Cancer Hospital
Hefei, Anfei, China
RECRUITINGLingying Wu
Beijing, Beijing Municipality, China
RECRUITINGPeking University Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGChongqing University cancer Hospital
Chongqing, Chongqing Municipality, China
Objective response rate (ORR) assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
ORR is 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 1.1.
Time frame: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
ORR assessed by independent review committee (IRC) according to RECIST 1.1
ORR is defined as the percentage of participants who achieved a BOR of confirmed CR or PR, assessed by IRC based on RECIST 1.1.
Time frame: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Duration of response (DoR) assessed by investigators and IRC according to RECIST 1.1
DoR is defined as the period from the first occurrence of CR or PR to progressive disease (PD) or death of any cause. If no PD or death after CR/PR, the cut-off date of progression-free survival (PFS) will be used.
Time frame: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Disease control rate (DCR) assessed by investigators and IRC according to RECIST 1.1
DCR is defined as the percentage of participants with BOR of confirmed CR, PR and stable disease (SD).
Time frame: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Progression-free survival (PFS) assessed by investigators and IRC according to RECIST 1.1
PFS is defined as the time from first dose or randomization (if any) to PD or death of any cause.
Time frame: From the first dose or randomization to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Overall survival (OS)
OS is defined as the time from the first dose or randomization (if any) to death of any cause.
Time frame: From the first dose or randomization to death or withdrawal from study, whichever came first, assessed up to 24 months.
ORR assessed by investigators (combined criteria incorporating RECIST 1.1 and Gynecological Cancer Intergroup [GCIG]) CA-125 criteria; Ovarian cancer only)
Defined as the proportion of subjects with confirmed CR or PR before progression as assessed by incorporating both RECIST 1.1 and GCIG CA-125 criteria.
Time frame: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
CA-125 response rate assessed by investigators according to GCIG CA-125 criteria (ovarian cancer only)
CA-125 response rate is defined as the proportion of subjects with GCIG CA-125 criteria defined CA-125 response, which will be assessed in a subset of subjects with a baseline CA-125 level of at least twice the ULN as evaluable.
Time frame: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
Incidence and severity of adverse events (AEs)
AEs will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. The incidence and severity of AEs will be calculated and summarized.
Time frame: From the first dose to 90 days after the end of treatment.
Observed maximum plasma concentration (Cmax) of HS-20089
Cmax will be obtained following administration of the first dose of HS-20089 during the first cycle.
Time frame: From pre-dose to 14 days after the first dose of HS-20089 on Cycle 1 (each cycle is 21 days).
Time to reach maximum plasma concentration (Tmax) of HS-20089 following the first dose
Tmax will be obtained following administration of the first dose of HS-20089 during the first cycle.
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-20089
Area under the plasma concentration versus time curve from time zero to the last sampling time when the concentration is no less than the lower limit of quantification (LLQ). AUC0-t will be 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).
Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) after single dose of HS-20089
AUC0-∞ will be calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
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-20089 in serum
Serum samples will be collected for the determination of anti-drug antibody (ADA) at designated time points.
Time frame: From the first dose to 90 days after the end of treatment.
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Fujian Cancer Hospital
Fuzhou, Fujian, China
RECRUITINGSun Yat-Sen Memorial Hospital Sun Yat-Sen University
Guangzhou, Guangdong, China
RECRUITINGGuangxi Cancer Hospital
Nanning, Guangxi, China
RECRUITINGHainan General Hospital
Haikou, Hainan, China
RECRUITINGThe fourth Hospital of Heibei Medical University
Shijiazhuang, Hebei, China
RECRUITINGHarbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
RECRUITING...and 18 more locations