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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer (mCRPC)
• Intervention / Treatment: Drug: YL201 for Injection

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sasha Stann; Phone Number: 06172408494; Email: sasha@medilinkthera.com
• Study Contact Backup: Name: Steve Chin, Ph.D.; Phone Number: 06178719455; Email: info@medilinkthera.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Site Coordinator
  • Anhui
    • Hefei, Anhui, China
      • Not yet recruiting
      • Anhui Provincial Hospital
      • Contact: Site Coordinator
  • Beijing
    • Peking, Beijing, China
      • Not yet recruiting
      • Peking University First Hospital
      • Contact: Site Coordinator
    • Peking, Beijing, China
      • Not yet recruiting
      • Peking University Third Hospital
      • Contact: Site Coordinator
  • Changsha
    • Hunan, Changsha, China
      • Not yet recruiting
      • Hunan Cancer Hospital
      • Contact: Site Coordinator
  • Chongqing
    • Chongqing, Chongqing, China
      • Not yet recruiting
      • Chongqing University Cancer Hospital
      • Contact: Site Coordinator
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Nanjing Drum Tower Hospital
      • Contact: Site Coordinator
    • Nantong, Jiangsu, China
      • Not yet recruiting
      • Nantong Tumor Hospital
      • Contact: Site Coordinator
  • Tianjin
    • Tianjin, Tianjin, China
      • Not yet recruiting
      • The Second Hospital Of Tianjin Medical University
      • Contact: Site Coordinator
  • Zhejiang
    • Ningbo, Zhejiang, China
      • Recruiting
      • Ningbo Yinzhou No.2 Hospital
      • Contact: Site Coordinator
    • Wenzhou, Zhejiang, China
      • Not yet recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Site Coordinator

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.	Drug: YL201 for Injection; Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.
Experimental: Part2; Patients will be treated with YL201 intravenous (IV) infusion at recommended dose of YL201 for the pivotal clinical study once every 3 weeks (Q3W) as a cycle.	Drug: YL201 for Injection; Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Recommended dose of YL201 for the pivotal clinical trial.		Approximately within 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease control Rate (DCR) by RECIST1.1 and PCWG3 criteria per investigators' review	Disease control rate	Approximately within 36 months
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
To evaluate TTR of YL201 in the treatment of mCRPC	Time to Objective response	Approximately within 36 months
To evaluate DpR of YL201 in the treatment of mCRPC	deepness of response	Approximately within 36 months
To evaluate TTPR of YL201 in the treatment of mCRPC	time to PSA response	Approximately within 36 months
To evaluate PDoR of YL201 in the treatment of mCRPC	PSA duration of response	Approximately within 36 months
To evaluate PDpR of YL201 in the treatment of mCRPC	PSA deepness of response	Approximately within 36 months
To evaluate TTPP of YL201 in the treatment of mCRPC	time to PSA progression	Approximately within 36 months
To evaluate TFST of YL201 in the treatment of mCRPC	time to first subsequent therapy	Approximately within 36 months
To evaluate rPFS of YL201 in the treatment of mCRPC	Radiographic Progression Free Survival	Approximately within 36 months
To evaluate OS of YL201 in the treatment of mCRPC	overall survival	Approximately within 36 months
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
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
To evaluate the Cmax of YL201	Maximum concentration: The highest measured concentration of YL201 in the bloodstream.	Approximately within 36 months
To evaluate the Ctrough of YL201	trough concentration	Approximately within 36 months
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
To evaluate the Vd of YL201	volume of distribution	Approximately within 36 months
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
To evaluate the immunogenicity of YL201		Approximately within 36 months
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
Expression of B7H3 in tumor tissue at baseline and the relationship with the efficacy of YL201.		Approximately within 36 months
Number of participants with AEs, SAEs, and SAEs leading to study treatment interruption or discontinuation.	adverse event, serious adverse event	Approximately within 36 months
To evaluate the E-R relationship of YL201	exposure-response	Approximately within 36 months

Collaborators and Investigators

• Sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: January 28, 2024
• First Submitted That Met QC Criteria: January 28, 2024
• First Posted (Actual): February 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: YL201-CN-201-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No