A Study of SHR2554 Alone or in Combination With SHR3680 in the Treatment of mCRPC

Study Overview
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Brief Summary
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The aim of this trial is to study the tolerance, pharmacokinetics (PK) and efficacy of SHR2554 alone or in combination with SHR3680 in the treatment of patients with metastatic Castration Resistant Prostate Cancer.

Detailed Description
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This is a multicenter, open, non-randomized and dose-escalating and -expansion Phase I/II trial and it studies the tolerance, PK and efficacy of SHR2554 alone or in combination with SHR3680 in the treatment of patients with metastatic Castration Resistant Prostate Cancer. The Phase I part is a dose-escalating study including Ia (dose-escalation monotherapy) and Ib (dose-escalation combination therapy). Approximately 18-30 patients in Phase Ia will only receive one of five dose levels of orally SHR2554. Approximately 30 48 patients in Phase Ib trial will receive SHR2554 combined with SHR3680, in which 2 3 different dose levels of SHR2554 will be selected based on the result of the Phase Ia. Phase II part is a dose-expansion study. Primary endpoints of the study are dose-limiting tolerance (DLT), maximum-tolerated dose (MTD) and prostate specific antigen (PSA) response rate.

Official Title
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A Phase I/II,Open-Label,Does-Escalation and -Expansion, Safety,Pharmacokinetics and Efficacy Study of SHR2554 Alone or in Combination With SHR3680 in the Treatment of Patients With Metastatic Castration Resistant Prostate Cancer

Conditions
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Prostate Cancer, Castration-resistant Prostate Cancer

Intervention / Treatment
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* Drug: SHR3680
* Drug: SHR2554


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed prostate cancer; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1; Radiographic evidence of metastasis; Sustained therapy of luteinizing hormone-releasing hormone analogue（LHRHA）or received bilateral orchiectomy; patients who did not receive bilateral orchiectomy are willing to receive sustained therapy of LHRHA; Evidence of prostate cancer progression under the sustained therapy of LHRHA or bilateral orchiectomy; Adequate hepatic, renal, heart, and hematological functions; Patients have given voluntary written informed consent before performance of any study-related procedure not part of normal medical care,with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Exclusion Criteria: Have received any anti-tumor therapy in the past 4 weeks,including radiotherapy, chemotherapy, operation, targeted therapy, immunotherapy, and endocrinotherapy; Planned to initiate any other anti-tumor therapies during the study; Unable to swallow, chronic diarrhea and intestinal obstruction, or the presence of a variety of other factors that affect drug use and absorption; Clinically significant cardiovascular diseases; History of seizure or certain conditions that may predispose to seizure; Severe concurrent disease and infection that, in the judgment of the investigator, would make the patient inappropriate for enrollment.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR2554<br>Participants will receive SHR2554 orally | Drug: SHR2554<br>* Tablet. Specifications of 50mg and 200mg<br>|
| Experimental: SHR2554+SHR3680<br>Participants will receive SHR2554 combined with SHR3680 orally | Drug: SHR3680<br>* Tablet. Specifications of 80mg<br>Drug: SHR2554<br>* Tablet. Specifications of 50mg and 200mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | A DLT is any of the predefined set of unacceptable adverse events observed and at least possibly related to investigational agents | Approximately 12 months | 
| MTD | The first cycle DLTs will be utilized to determine the MTD and future dose escalations or de-escalations The first cycle DLTs will be utilized to determine the MTD and future dose escalations or de-escalations | Approximately 12 months | 
| PSA response rate | After the continuous therapy from randomisation to the end of the 12 weeks, the ratio of patients whose levels of PSA decreased more than 50% | Approximately 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to PSA progression | Time from randomisation to the first time of PSA progression according to the criteria of the Prostate Cancer Clinical Trials Working Group 3 （PCWG3) | Approximately 70 months | 
| Objective response rate (ORR) | The percentage of subjects with measureable disease at baseline who achieved a complete or partial response in their soft tissue disease using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria | Approximately 70 months | 
| Under the Curve (AUC) | The single dose and multiple dose PK will be calculated as data permits including Area AUC | Approximately 12 months | 
| Maximum Observed Plasma Concentration (Cmax) | The single-dose and multiple dose PK will be calculated as data permits including Cmax | Approximately 12 months | 
| Adverse events (AE) | The type, frequency, severity, timing, seriousness, and relationship to study therapy | Approximately 70 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Castration-resistant Prostate Cancer, SHR2554, SHR3680