Study of HRS-2189 Combined HRS-5041 in Prostate Cancer

A Phase II Study of HRS-2189 Combined HRS-5041 in Metastatic Prostate Cancer

Our study is aimed to evaluate the efficacy and safety of HRS-2189 combined with HRS-5041 in metastatic prostate cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer Metastatic Disease
• Intervention / Treatment: Drug: HRS-2189; Drug: HRS-5041

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dingwei Ye, Chief physician; Phone Number: +8621-64175590; Email: dwyeli@163.com
• Study Contact Backup: Name: Shanshan Wang, Attending physician

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200230
      • Fudan Cancer Hospital
      • Contact: Dingwei Ye, Chief physician; Phone Number: +8621-64175590; Email: dwyeli@163.com
      • Contact: Shanshan Wang, Attending physician
      • Contact: Dingwei Ye, Chief physician

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years to 80 years old (including boundary values), male subjects;
• ECOG PS Score: 0~1;
• Histologically or cytologically confirmed prostate adenocarcinoma, and no prior diagnosed as neuroendocrine carcinoma or small cell carcinoma;
• Disease progression when enrolled in the study;
• Confirmed metastatic disease by CT/MRI/99mTc radioactive bone scan;
• Subjects must have a life expectancy ≥ 3 months;
• Adequate organ function and marrow function (no corrective treatment within 14 days before first dose);
• Male subjects who have partner of childbearing potential should agree to take action of contraception and avoid to donate sperm;
• Willing and able to provide written informed consent and comply with the requirements and restrictions in the protocol.

Exclusion Criteria:

• Known existence of CNS metastasis or meningeal metastasis, or known history of primary CNS tumor;
• Severe bone injury caused by bone metastasis identified by investigators, including uncontrolled severe bone pain, pathological bone fracture at the important part and spinal cord compression having occurred for the last 6 months or expected to occur in the near future;
• Existence of third space fluid that is not well controlled by effective methods, e.g. drainage;
• Has received antitumor surgery, radiotherapy, chemotherapy, targeted therapy, immunological therapy or attenuated live vaccine within 4 weeks before first dose of study therapy (6-week washout period for bicalutamide);
• Has been enrolled in other clinical trials within 4 weeks before first dose of study therapy;
• Use of other antitumor treatment during the study;
• Damage caused by any prior anti-tumor treatment has not recovered to ≤ grade 1 or criteria specified by this study (per NCI-CTCAE 5.0; except alopecia or other tolerable adverse events identified by investigators);
• Uncontrolled hypertension, or prior hypertensive crisis or history of hypertension;
• Existence of arterial/venous thrombotic event within 6 months before first dose, such as cerebrovascular accidents (including transient ischemic attack, cerebral haemorrhage and cerebral infarction), deep venous thrombosis and pulmonary embolism;
• Existence of one of multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea and bowel obstruction), or active gastrointestinal disease or other diseases which may obviously affect distribution of drug absorption, metabolism or excretion;
• Has active hepatitis B (HBsAg-positive and HBV DNA≥500 IU/mL), hepatitis C (positive for HCV antibody and HCV RNA above ULN) and hepatic cirrhosis;
• Has an active infection requiring antibiotics, antiviral or antifungal treatment, or pyrexia >38.5℃ of unknown origin during the screening period before first dose of study therapy (patients with pyrexia due to cancer could be enrolled determined by investigator);
• Subjects with innate or acquired immunodeficiency (such as HIV infection); Known history of allogeneic organ transplantation or hematopoietic stem cell transplantation;
• Other malignancy within prior 3 years before first dose of study therapy, except curatively treated cancer, including radical therapy-treated skin basal cell carcinoma or skin squamous cell carcinoma, papillary thyroid carcinoma, or any type of in situ carcinoma with complete excision, such as in situ cancer of the cervix, ductal carcinoma in situ of breast;
• Hypersensitivity to study therapy or any of its excipients;
• Uncontrolled cardiovascular clinical symptom or disease within 6 months before first dose of study therapy;
• Other conditions that might influence the study and analysis of results in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HRS-2189 + HRS-5041; All subjects enrolled will receive HRS-2189 + HRS-5041 combination therapy.	Drug: HRS-2189; HRS-2189; Drug: HRS-5041; HRS-5041

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA50	PSA50 is the percentage of evaluable patients with ≥50% decline in PSA level, measured at baseline and the time point of every 4 weeks in efficacy analysis set.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA30	PSA30 is the percentage of evaluable patients with ≥30% decline in PSA level measured at baseline and the time point of every 4 weeks in efficacy analysis set.	up to 2 years
Time to PSA progression	The definition is the time from the date of first dose until the date of first PSA progression or death (by any cause in the absence of progression). PSA progression is per PCWG3 criteria and newest version of CSCO guideline as follows: 1) if PSA level declines from baseline, PSA level is ≥25% increase from baseline and ≥1 ng/ml, which needs to be confirmed after at least 4 weeks; 2) if PSA level has not declined from baseline, PSA level is ≥25% increase from baseline and ≥1 ng/ml after at least 12 weeks from the date of first dose.	up to 2 years
ORR by investigator	ORR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response) or PR (partial response) per RECIST v1.1, and measured at baseline and the time point of every 8 weeks in first 16 weeks, at the time point of every 12 weeks after first 16 weeks.	up to 2 years
DCR by investigator	DCR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response), PR (partial response) or SD (stable disease) per RECIST v1.1, and measured at baseline and the time point of every 8 weeks in first 16 weeks, at the time point of every 12 weeks after first 16 weeks.	up to 2 years
DoR	DoR is the time from the date of first detection of objective response (which is subsequently confirmed) until the date of objective radiographic disease progression.	up to 2 years
rPFS	rPFS is the time from the date of first dose until the date of objective radiographic disease progression or death (by any cause in the absence of progression) per RECIST v1.1 and PCWG3 criteria.	up to 2 years
Time to next skeletal-related event	The definition is the time from the date of first dose until the date of next skeletal-related event. Skeletal-related events include radiotherapy or surgery to the bone, pathological bone fracture, spinal cord compression, or changing anti-tumor treatment in order to relieve bone pain.	up to 2 years
OS	OS is the time from the date of first dose until the date of death by any cause.	up to 2 years
Percentage of participants who experience an adverse event [Safety and Tolerability]	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Percentage of participants who experience an adverse event and discontinue study drug due to an AE.	From the time of informed consent provided to 30 days after the last dose of study therapy

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Dingwei Ye, Chief physician, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Prostatic Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: CRPC-MUL-IIT-HRS2189-HRS5041

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No