Dalpiciclib Isethionate Tablets Combined With Abiraterone Acetate Tablets (I) and Prednisone Tablets (AA-P) Versus Placebo Combined With AA-P in Treatment of High-volume, Metastatic, Hormone-sensitive Prostate Cancer (mHSPC)

Study Overview
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Brief Summary
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This study was to evaluate the safety and efficacy of dalcilide tablets in combination with AA-P in the treatment of subjects with high tumor burden mHSPC and to determine the second stage starting dose and progression-free survival（rPFS） based on BICR assessment

Official Title
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A Multicenter, Randomized, Double-blind Phase Ib/III Clinical Study of Dalpiciclib Isethionate Tablets Combined With Abiraterone Acetate Tablets (I) and Prednisone Tablets (AA-P) Versus Placebo Combined With AA-P in Treatment of High-volume, Metastatic, Hormone-sensitive Prostate Cancer (mHSPC).

Conditions
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High-volume, Metastatic, Hormone-sensitive Prostate Cancer (mHSPC)

Intervention / Treatment
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* Drug: dalpiciclib isethionate tablets; abiraterone acetate tablets; prednisone tablets
* Drug: placebo; abiraterone acetate tablets; prednisone tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of ≥ 18 years old,male ECOG PS score of 0 or 1； Prostate adenocarcinoma confirmed by histological。 ADT no more than 3 months prior to randomization (when docetaxel is not used) with no radiographic or PSA progression Receiving or maintaining androgen deprivation therapy (ADT) during the planned study period, i.e. continuous treatment with luteinizing hormone-releasing hormone analogues (LHRHA) (drug castration) or prior bilateral orchiectomy (surgical castration) Voluntarily participate in this clinical trial, understand the study procedure and have signed informed consent Exclusion Criteria: Previous ADT, chemotherapy, surgery, external radiation exposure, brachytherapy, radiopharmaceuticals, or experimental topical treatments (eg, radiofrequency ablation, cryoponic, high-energy focused ultrasound) for prostate cancer Previous use of CDK4/6 inhibitors (such as piperaciclib, rebocillib and abeceptil), second-generation androgen receptor antagonists (such as enzalutamide, apatamide, darotamide, revilumide and proclomide, etc.), ketoconazole, abiraterone acetate or other investigational drugs that inhibit androgen synthesis (such as TAK-700), other anti-tumor biological therapy, targeted therapy or tumor immunotherapy Confirmed by imaging, there are brain tumor foci History of severe lung disease such as interstitial pneumonia Plan to receive any other antitumor therapy during this trial Inability to swallow, chronic diarrhea and intestinal obstruction, or other factors that affect drug taking and absorption

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dalpiciclib+ abiraterone+ prednisone<br> | Drug: dalpiciclib isethionate tablets; abiraterone acetate tablets; prednisone tablets<br>* dalpiciclib+ abiraterone+ prednisone<br>|
| Placebo Comparator: placebo+abirarerone+prenisone<br> | Drug: placebo; abiraterone acetate tablets; prednisone tablets<br>* placebo+abirarerone+prenisone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event (AE) incidence |  | approximately 63 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK： Steady-state trough concentrations of Dalsili and Abiraterone (Cmin, ss) |  | approximately 6 months | 
| rPFS | Time from randomisation to radiologically confirmed progressive disease or death due to any cause | approximately 63 months | 
| PSA response rate | In patients who had not started androgen deprivation prior to randomization, the proportion of patients whose PSA levels were ≥ 90% lower than baseline by the end of the study treatment week | approximately 63 months | 
| ORR | Objective response rate+ The proportion of participants evaluated according to RECIST v1.1 and PCWG3 criteria that achieved predetermined tumor volume reduction and maintained the minimum duration was the sum of the proportion of complete and partial responses | approximately 63 months | 
| Time to PSA progression | Time from randomisation to the first time of PSA progression | approximately 63 months |