A Phase 1 Dose Escalation and Expansion Study Of SHR7280 In Subjects With Hormone Sensitive Prostate Cancer

Study Overview
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Brief Summary
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This is an open-label, multicenter, dose escalation and expansion Phase 1 study of SHR7280 in adult patients with hormone sensitive prostate cancer.

Official Title
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An Open-Label, Multicenter, Dose Escalation And Expansion Study Of SHR7280 In Subjects With Hormone Sensitive Prostate Cancer

Conditions
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Hormone Sensitive Prostate Cancer

Intervention / Treatment
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* Drug: SHR7280


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent document； Age ≥18 years old; Histologically or cytologically confirmed prostate adenocarcinoma; Candidate for androgen deprivation therapy (ADT) for the management of hormone-sensitive prostate cancer； Appropriate serum testosterone and serum PSA concentration at screening as specified in the protocol； Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1; Adequate organ performance based on laboratory blood tests; Agree to use adequate contraception prior to study entry and for the duration of study participation. Exclusion Criteria: Previously received gonadotropin-releasing hormone analogues (GnRH-a) for more than 12 months total duration (if GnRH-a was received for 12 months or less, then that GnRH-a must have been completed washout period prior to the first dose of study drug). Patients who have received chemotherapy for prostate cancer; History of surgical castration; Received Abiraterone acetate with 3 months prior to the first dose of study drug; Receieved molecular target therapy, immunotherapy, androgen receptor blockade, 5-alpha reductase inhibitors, estrogen, and other investigational compound with 4 weeks prior to the first dose of study drug; Patients with known or suspected brain metastasis； Diagnosis or treatment for another systemic malignancy within 5 years before study treatment initiation; Patients with uncontrolled and clinically significant hypertension and diabetes; Known hypersensitivity to SHR7280, SHR7280 excipients,； History of immunodeficiency (including HIV infection) or organ transplantation; Known active hepatitis B or C infection; Other serious accompanying illnesses, which, in the researcher's opinion, could seriously adversely affect the safety of the treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, Multicenter, Singel Group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR7280 Does Escalation and Expansion<br> | Drug: SHR7280<br>* Drug: SHR7280 All participants receive SHR7280 alone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events（AEs） |  | 30 days after last dose | 
| Dose Limited Toxicity (DLT) |  | 28 Days (first cycle) | 
| Maximum tolerable dose (MTD) |  | 28 Days (first cycle） | 
| Recommended dose for phase II (RP2D) |  | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration time curve in the dosing interval AUC(TAU) of SHR7280 |  | 30 days after last dose | 
| Maximum observed plasma concentration (Cmax) of SHR7280 |  | 30 days after last dose | 
| Observed trough plasma concentration (Ctrough) of SHR7280 |  | 30 days after last dose | 
| Time of maximum observed plasma concentration (Tmax) of SHR7280 |  | 30 days after last dose | 
| Serum testosterone concentrations |  | 30 days after last dose | 
| Serum luteinizing hormone (LH) concentrations |  | 30 days after last dose | 
| Serum follicle stimulating hormone (FSH) concentrations |  | 30 days after last dose | 
| Time to Achieve Testosterone Concentrations < 50 ng/dL |  | 30 days after last dose | 
| Percentage of Participants With Effective Castration Rate Over 24 Weeks |  | Day 1 of Week 5 to Day 1 of Week 25 | 
| Percentage of Participants With Effective Castration Rate Over 48 Weeks |  | Day 1 of Week 5 to Day 1 of Week 49 | 
| Percentage of Serum Prostate-Specific Antigen Concentration Change frome Baseline at the End of Weeks 4, 8, 12 |  | Day 1 of Weeks 5, 9 and 13 | 
| Time to Prostate-Specific Antigen Progression |  | 30 days after last dose |