Advanced Prostate Cancer
Conditions
Keywords
Advanced prostate cancer, B7H3, HS-20093
Brief summary
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.
Interventions
Sponsors
Hansoh BioMedical R&D Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men greater than or equal to 18 years. * Voluntarily to participate, Signed and dated Informed Consent Form. * Patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after at least one type of novel hormonal therapy (standard treatment). * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\ 1. * Estimated life expectancy ≥ 12 weeks. * Men should use adequate contraceptive measures throughout the study, up to 3 months after the last dose of HRS-5041 or 4.5 months after the last dose of HS-20093 (whichever is later).
Exclusion criteria
* Treatment with any of the following: a. Previous or current treatment with B7-H3 targeted therapy. b. Previous treatment with AR PROTAC. c. Any cytotoxic chemotherapy, investigational agents and anticancer drugs within 21 days prior to the first scheduled dose of HS-20093+HRS-5041. d. brain metastases. * Any unresolved toxicities from prior therapy greater than Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. * History of other primary malignancies. * Inadequate bone marrow reserve or organ dysfunction. * Severe, uncontrolled or active cardiovascular diseases. * Severe or uncontrolled diabetes. * The presence of active infectious diseases. * Any known or suspected interstitial lung disease. * History of serious neuropathy or mental disorders. * History of severe hypersensitivity reaction, severe infusion reaction. * Hypersensitivity to any ingredient of HS-20093. * Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator. * Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the maximum tolerated dose (MTD) or Maximum Administrated dose (MAD) | 21 days from administration of the first dose (C1D1) in the dose escalation phase， assessed up to 24 months | Number of participants with dose limiting toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the maximum plasma concentration (Cmax) | up to approximately 24 months | Cmax will be obtained following administration of the first dose of HS-20093 during the first cycle |
| To evaluate the Time to reach maximum plasma concentration (Tmax) | up to approximately 24 months | Tmax will be obtained following administration of the first dose of HS-20093 during the first cycle |
| To evaluate the Area under plasma concentration versus time curve from zero to last sampling time (AUC) | up to approximately 24 months | 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 |
| To evaluate the immunogenicity of HS-20093 | up to approximately 24 months | Proportion of patients who are positive for anti-HS-20093 antibodies |
| To evaluate the incidence and severity of adverse events (AEs) | 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) | 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. |
| To evaluate the Disease control rate (DCR) determined by investigators according to RECIST 1.1 and PCWG3 | up to approximately 24 months | 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) \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks); SD shall be assessed at least 5 weeks after the first dose\] |
| To evaluate the Duration of response (DoR) determined by investigators according to RECIST 1.1 and PCWG3 | up to approximately 24 months | 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 \[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\] |
| To evaluate the Prostate-specific Cancer Antigen (PSA) response rate（PSA30,PSA50,PSA90） | up to approximately 24 months | PSA response is defined as a ≥ 30%，≥ 50% ，≥ 90% decline in PSA from baseline with PSA confirmation ≥ 3 weeks after the first documented reduction |
| To evaluate the Time to PSA progression | up to approximately 24 months | 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. |
| To evaluate the ORR determined by investigators | up to approximately 24 months | 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) |
Countries
China
Outcome results
None listed