Clinical trial NCT06568094: A Study of HRS-5041 Tablets Combined With Antitumor Therapy in Subjects With Advanced Prostate Cancer
Official title: An Open, Multicenter Phase Ib/II Study on the Safety, Tolerability and Efficacy of HRS-5041 Tablets Combined With Antitumor Therapy in Subjects With Advanced Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-23
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: HRS-5041 tablets combined with antitumor therapy
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, and safety of HRS-5041 tablets combined with antitumor therapy in subjects with advanced prostate cancer.


Eligibility criteria: Inclusion Criteria:

1. Have the ability to give informed consent, and are willing and able to comply with planned visits for medical examinations and other procedural requirements.
2. The age is above 18 years old when signing the informed consent (the ceiling age is 80 years old in the dose escalation phase), male.
3. ECOG score is 0 or 1.
4. An expected survival of ≥ 12 weeks.
5. Adenocarcinoma of the prostate confirmed with histologically or cytologically ,and without a diagnosis of neuroendocrine or small cell carcinoma.
6. Adequate blood samples should be provided for gene mutation detection during the screening period. It is recommended to provide tumor tissue samples.
7. Male subjects whose partner is women of childbearing potential (WOCBP) are required to use highly effective contraception from the date of signing the informed consent until 3 months after the last dose of the investigational drug.

Exclusion Criteria:

1. Plan to receive any other antitumor therapy during this study.
2. Had history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML); Or had other malignancies in the 5 years prior to the first dose.
3. Participants who are participating in another clinical study or whose first dose is less than 4 weeks from the end of the previous clinical study (last dose), or five half-lives of the investigational drug, whichever is shorter.
4. Had undergone major surgery within 28 days prior to first dosing; Minor traumatic surgery within 7 days prior to first dosing; There are non-healing wounds, untreated fractures.
5. Drugs with a strong inducer or inhibitor of the metabolic enzyme CYP3A have been used in the past, and the washout period from the end time to the first administration in this study is shorter than the 5 half-life of the drug.
6. The toxicity from previous anti-tumor treatment has not recovered to ≤ grade I.
7. Central nervous system or meningeal metastasis of tumors is known or subjects have a history of primary central nervous system tumors.
8. Severe cerebrovascular disease occurred within 6 months prior to administration.
9. Subjects with poorly controlled hypertension and a history of hypertensive crisis or hypertensive encephalopathy.
10. Severe bone injury due to bone metastases, pathological fractures , and spinal cord compression as determined by the investigators at important sites that occurred within the last 6 months or are expected to occur in the near future.
11. Having one of multiple factors that affect the oral drug or having an active gastrointestinal disease or other disease that may significantly affect drug absorption, distribution, metabolism, or excretion.
12. Had history of allergy to the proposed investigational drug or its excipient components.
13. Presence of active heart disease in the 6 months prior to first dosing, including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, and medically treatable ventricular arrhythmias.
14. Presence of active hepatitis B and hepatitis C; Or serious infected persons requiring antibiotics, antivirals or antifungal drugs to control.
15. Presence of the history of immunodeficiency or organ transplantation.
16. Presence of other serious physical or mental diseases or laboratory abnormalities.

Primary outcomes:
measure: Recommended phase II dose (Phase Ib)
timeFrame: 21 or 28 days
measure: Incidence and severity of adverse events (AE) (Phase Ib)
timeFrame: 2 years
measure: PSA response rate (Phase II)
timeFrame: 1 year
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 1 year
measure: Disease control rate (DCR)
timeFrame: 1 year
measure: Duration of response (DoR)
timeFrame: 1 year
measure: PSA response rate
timeFrame: 1 year
measure: Time to PSA progression
timeFrame: 1 year
measure: Radiographic progression-free survival (rPFS)
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 2 years
measure: Blood concentrations of HRS-5041
timeFrame: 16 weeks
measure: Blood concentrations of HRS-1167
timeFrame: 16 weeks
measure: Blood concentrations of SHR2554
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Ha'erbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine, Renji Hospital
state: Shanghai
Study officials:
References: