A Phase II Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Patients With mCRPC

Metastatic Castration-resistant Prostate Cancer (mCRPC) Clinical Trial

Official title:

A Multicenter, Open-Label, Phase II Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Patients With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06241846
• Other study ID #: YL201-CN-201-01
• Status: Recruiting
• Phase: Phase 2
• Start date: February 22, 2024
• Est. completion date: February 2029

Study information

• Verified date: April 2024
• Source: MediLink Therapeutics (Suzhou) Co., Ltd.
• Contact: Sasha Stann
• Phone: 06172408494
• Email: sasha[@]medilinkthera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, open-label, Phase 2 study. The study will enroll subjects with metastatic castration-resistant prostate cancer (mCRPC) previously treated with at least 1 prior line of novel hormone therapy (NHT). NHT includes abiraterone, enzalutamide, apalutamide, darotamide, or rezvilutamide. Subjects must have received no more than 2 prior lines of taxane-containing regimen.

This study consists of two parts. Part 1 will preliminarily assess the efficacy and tolerability of YL201 at 2.0, 2.4, or 2.8 mg/kg with approximately 40 subjects. Part 2 will further assess the efficacy and safety of YL201 at the recommended expansion dose (RED) obtained from Part 1 with up to 60 subjects.

YL201 will be administered intravenously (IV) on Day 1 of each 3-week cycle until criteria of treatment discontinuation are met. Subjects will undergo regular testing for signs of disease progression (PD) using computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scan, and prostate-specific antigen (PSA) blood test. Routine examinations and blood tests will be performed and evaluated by the study physician.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 2029
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subjects who understand relevant information of the study prior to initiation of the study and voluntarily sign and date on the ICF.

2. Age = 18 years.

3. Patients who are histologically or cytologically confirmed prostate cancer.

4. Patients with metastatic lesions confirmed by CT, MRI, or bone scan imaging within 28 days prior to the first dose.

5. Patients with archived or fresh tumor tissue samples. Patients who cannot provide tumor samples or cannot provide sufficient samples may be enrolled in this study after considering specific circumstances and discussions with the Sponsor.

6. Eastern cooperative oncology group performance status (ECOG PS) score of 0 or 1.

7. The function of organs and bone marrow meets the requirements within 7 days prior to the first dose.

8. Patients must agree to adopt highly effective contraceptive measures from screening, throughout the study period, and within at least 6 months after the last dose of the investigational drug.

9. Expected survival = 6 months.

10. Be capable of and willing to comply with the visits and procedures stipulated in the study protocol.

Exclusion Criteria:

1. Previously treated with drugs targeting B7H3.

2. Currently participating in another clinical study, unless it is an observational (non-interventional) clinical study, or the patient is at the follow-up period of an interventional study.

3. Previously treated with topoisomerase I inhibitors or ADC therapy composed of topoisomerase I inhibitors.

4. The washout period of the previous anti-tumor therapy is considered insufficient.

5. Patients received major surgery.

6. Prior treatment with allogeneic bone marrow transplantation or solid organ transplantation.

7. Prior treatment with glucocorticoids for more than 28 consecutive days within 28 days prior to the first dose of the investigational drug.

8. Patients received any live vaccine within 4 weeks prior to the first dose of the investigational drug, or plan to receive live vaccine during the study period.

9. Have pathological long bone fracture, or the risk of pathological long bone fracture.

10. Have meningeal metastasis or cancerous meningitis.

11. Have uncontrolled bladder outlet obstruction or urinary incontinence.

12. Have brain metastasis or spinal cord compression.

13. Patients with uncontrolled or clinically significant cardiovascular diseases.

14. Clinically significant complicated pulmonary disorders.

15. Diagnosed with Gilbert's syndrome.

16. Accompanying uncontrolled effusion in the third space requiring repeated drainage.

17. Medical history of gastrointestinal perforation and/or fistula within 6 months prior to the first dose, or active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal diseases that may cause hemorrhage or perforation in the opinion of the investigator.

18. Active serious infection (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] = 3) within 4 weeks prior to the first dose.

19. Known human immunodeficiency virus (HIV) infection.

20. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

21. Diagnosed with the other malignancies that may change the expected survival or affect the response evaluation.

22. Unresolved toxicity of previous anti-tumor therapy.

23. History of severe hypersensitivity to inactive ingredients in the drug substance and drug product or other monoclonal antibodies.

24. Have any diseases, medical conditions, organ system dysfunction, or social conditions that may interfere with the subject ability to sign the ICF, adversely affect the subject ability to cooperate and participate in the study, or affect the interpretation of study results, including but not limited to mental illness or substance/alcohol abuse, in the opinion of the investigator.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer (mCRPC)
• Prostatic Neoplasms

Intervention

Drug:
• YL201 for Injection
Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.

Locations

Country	Name	City	State
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Chongqing University Cancer Hospital	Chongqing	Chongqing
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The Second Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Hunan Cancer Hospital	Hunan	Changsha
China	Shandong Tumor Hospital	Jinan	Shandong
China	Nanjing Drum Tower hospital	Nanjing	Jiangsu
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Ningbo Yinzhou No.2 Hospital	Ningbo	Zhejiang
China	Peking University First Hospital	Peking	Beijing
China	Peking University Third Hospital	Peking	Beijing
China	Fudan University Shanghai Cancer Center	Shanghai
China	Zhongshan Hospital of Fudan University	Shanghai	Shanghai
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	The First Affiliated Hospital of China Medical University	Shenyang	Liaoning
China	The Second Hospital of Tianjin Medical University	Tianjin	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Union Hospital of Huazhong University of Science and Technology Tongji Medical College	Wuhan	Hubei
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
MediLink Therapeutics (Suzhou) Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR) by RECIST1.1 and PCWG3 criteria per investigators' review	defined as percentage of participants with confirmed best overall response of confirmed complete response (CR) or partial response (PR) to treatment	Approximately within 36 months
Primary	Radiographic progression free survival (rPFS), and rPFS rate at 3/6 months by RECIST1.1 and PCWG3 criteria per investigators' review	defined as the time from the date of first administration to first documented progressive disease (PD) per RECIST1.1 and PCWG3 or death from any cause, whichever occurs first.	Approximately within 36 months
Primary	Recommended dose of YL201 for the pivotal clinical trial.		Approximately within 36 months
Secondary	disease control Rate (DCR) by RECIST1.1 and PCWG3 criteria per investigators' review	Disease control rate	Approximately within 36 months
Secondary	To evaluate DoR by RECIST1.1 and PCWG3 criteria per investigators' review of YL201 in the treatment of mCRPC	Duration of rasponse	Approximately within 36 months
Secondary	To evaluate TTR of YL201 in the treatment of mCRPC	Time to Objective response	Approximately within 36 months
Secondary	To evaluate DpR of YL201 in the treatment of mCRPC	deepness of response	Approximately within 36 months
Secondary	To evaluate PSA50 response rate and PSA50 response rate at 12 weeks of YL201 in the treatment of mCRPC	PSA50 response is defined as a = 50% decline in PSA from baseline with PSA confirmation = 3 weeks after the first documented reduction in PSA of = 50%.	Approximately within 36 months
Secondary	To evaluate TTPR of YL201 in the treatment of mCRPC	time to PSA response	Approximately within 36 months
Secondary	To evaluate PDoR of YL201 in the treatment of mCRPC	PSA duration of response	Approximately within 36 months
Secondary	To evaluate PDpR of YL201 in the treatment of mCRPC	PSA deepness of response	Approximately within 36 months
Secondary	To evaluate TTPP of YL201 in the treatment of mCRPC	time to PSA progression	Approximately within 36 months
Secondary	To evaluate TFST of YL201 in the treatment of mCRPC	time to first subsequent therapy	Approximately within 36 months
Secondary	To evaluate rPFS of YL201 in the treatment of mCRPC	Radiographic Progression Free Survival	Approximately within 36 months
Secondary	To evaluate OS of YL201 in the treatment of mCRPC	overall survival	Approximately within 36 months
Secondary	To evaluate time to first symptomatic skeletal event of YL201 in the treatment of mCRPC	assessed by investigator according to RECIST v1.1 and PCWG3 criteria	Approximately within 36 months
Secondary	Expression of B7H3 in tumor tissue at baseline and the relationship with the efficacy of YL201.		Approximately within 36 months
Secondary	Number of participants with AEs, SAEs, and SAEs leading to study treatment interruption or discontinuation.	adverse event, serious adverse event	Approximately within 36 months
Secondary	To evaluate the AUC of YL201	the area under curve: AUC is the total amount of YL201 in bloodstream after drug administration	Approximately within 36 months
Secondary	To evaluate the Cmax of YL201	Maximum concentration: The highest measured concentration of YL201 in the bloodstream.	Approximately within 36 months
Secondary	To evaluate the Ctrough of YL201	trough concentration	Approximately within 36 months
Secondary	To evaluate the CL of YL201	Clearance: defined as the amount of drug removed from the bloodstream by the body per unit of time	Approximately within 36 months
Secondary	To evaluate the Vd of YL201	volume of distribution	Approximately within 36 months
Secondary	To evaluate the T1/2 of YL201	Terminal half-life: defined as the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%	Approximately within 36 months
Secondary	To evaluate the E-R relationship of YL201	exposure-response	Approximately within 36 months
Secondary	To evaluate the immunogenicity of YL201		Approximately within 36 months