A Trial of SHR3680 in Prostate Cancer Patients Who Are Candidates for Radical Prostatectomy

Study Overview
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Brief Summary
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The study is being conducted to evaluate the efficacy and safety of SHR3680 plus androgen deprivation therapy (ADT) vs. placebo plus ADT in patients with high-risk localized or locally advanced prostate cancer using pathologic complete response (pCR) rate and metastasis-free survival (MFS).

Official Title
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A Phase III Randomized, Placebo-Controlled, Double-Blind Study of SHR3680 Plus Androgen Deprivation Therapy (ADT) Versus ADT in Patients With High-Risk Localized or Locally Advanced Prostate Cancer Undergoing Radical Prostatectomy

Conditions
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Patients With High-risk Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy

Intervention / Treatment
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* Drug: SHR3680
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of ≥ 18 years old; ECOG PS score of 0 or 1; Pathologically diagnosed as prostate adenocarcinoma; High-risk patients No distant metastasis (clinical staging of M0) as determined by BICR of imaging examinations; Subjects who are candidates for and plan to undergo radical prostatectomy (removal of the entire prostate and seminal vesicle plus pelvic lymphadenectomy); Exclusion Criteria: Subjects who received any prior treatment for prostate cancer, except medical ADT and/or first-generation androgen receptor antagonists (such as bicalutamide) for not more than 4 weeks; Subjects who received any other investigational products or underwent major surgery within 4 weeks prior to randomization; Subjects who are planning bilateral orchidectomy during the treatment period of the study; Subjects with dysphagia, chronic diarrhea, intestinal obstruction, or other factors affecting drug intake and absorption; Subjects with a history of epilepsy, or diseases that can induce seizures occurred within 12 months prior to randomization (including a history of transient ischemic attack, stroke, traumatic brain injury, and cognitive impairment, requiring hospitalization); Subjects with active heart disease within 6 months prior to randomization, including: severe/unstable angina pectoris, myocardial infarction, symptomatic congestive heart failure, and ventricular arrhythmias requiring medical 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: SHR3680 + ADT compared with placebo + ADT
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group：SHR3680 + ADT<br> | Drug: SHR3680<br>* Treatment group: SHR3680 240 mg orally once daily before or after breakfast, 28 days per cycle for a total of 12 treatment cycles (6 cycles before and 6 cycles following radical prostatectomy). Goserelin acetate sustained-release depot: 10.8 mg administered subcutaneously into the anterior abdominal wall once every 3 cycles (12 weeks) for a total of 12 cycles.<br>|
| Placebo Comparator: Treatment group : Placebo + ADT<br> | Drug: Placebo<br>* Treatment group ：Placebo 240 mg orally once daily before or after breakfast, 28 days per cycle for a total of 12 treatment cycles (6 cycles before and 6 cycles following radical prostatectomy). Goserelin acetate sustained-release depot: 10.8 mg administered subcutaneously into the anterior abdominal wall once every 3 cycles (12 weeks) for a total of 12 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR rate (assessed by pathology BICR) | Defined as the proportion of subjects with no residual tumor detected in prostatectomy specimens by H&E staining and ancillary immunohistochemistry (if necessary) as assessed by pathology BICR. | 36 months since the first subject will be enrolled. | 
| MFS (assessed by imaging BICR). | Defined as the time from the date of randomization to the date of first occurrence of BICR-confirmed radiographic distant metastasis, accidental pathologic finding of distant metastasis, or death from any cause (whichever occurs first), regardless of whether the subject reveives any other anti-tumor therapy or has missing (or unevaluable) tumor assessments. | 84 months since the first subject will be enrolled. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MFS (investigator-assessed). | Defined as the time from the date of randomization to the date of first occurrence of investigator-assessed radiographic distant metastasis to the bone or soft tissue, accidental pathologic finding of distant metastasis, or death from any cause (whichever occurs first), regardless of subsequent anti-tumor treatment or missing (or unevaluable) tumor assessments. | 84 months since the first subject will be enrolled. | 
| PSA response rate. | Defined as the proportion of subjects with a ≥ 90% decrease in PSA levels from baseline on Day 1 of Cycle 4. | 25 months since the first subject will be enrolled. | 
| PSM rate. | Defined as the proportion of subjects without tumor cells detected in the margin of prostatectomy pathological specimens following H&E staining and ancillary immunohistochemistry (if necessary), as assessed by local pathologists. | 31 months since the first subject will be enrolled. | 
| Time to BCR. | Defined as the time from the date of randomization to the time of BCR (i.e. two consecutive PSA rise ≥ 0.2 ng/mL following radical prostatectomy). | 42 months since the first subject will be enrolled. |