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

Phase 2

Recruiting

Conditions: Metastatic Castration-resistant Prostate Cancer (mCRPC)

Interventions: Drug: YL201 for Injection

Registration Number: NCT06241846

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

Brief Summary: This is a multicenter, open-label, phase II study of YL201 in China to evaluate the efficacy, safety, and PK characteristics of YL201 on mCRPC.

Detailed Description: Not available

Recruitment & Eligibility

Status: RECRUITING

Sex: Male

Target Recruitment: 100

Inclusion Criteria

Subjects who understand relevant information of the study prior to initiation of the study and voluntarily sign and date on the ICF.
Age ≥ 18 years.
Patients should meet the following conditions to be enrolled:
- Histologically or cytologically confirmed prostate cancer. Note: The primary histological classification indicated by biopsy should be adenocarcinoma;
- Meeting the following criteria for clinical diagnosis of mCRPC:

Subjects who understand relevant information of the study prior to initiation of the study and voluntarily sign and date on the ICF.
Age ≥ 18 years.
Patients should meet the following conditions to be enrolled:

• Histologically or cytologically confirmed prostate cancer. Note: The primary histological classification indicated by biopsy should be adenocarcinoma;

• Meeting the following criteria for clinical diagnosis of mCRPC:

√Testosterone level after castration (a serum testosterone level of <50 ng/dl or 1.7 nmol/L);
- Serum prostate specific antigen (PSA) progression (PSA > 1 ng/mL and 2 consecutive increases in PSA with at least a 1-week interval >50% from baseline), or PD by imaging (≥ 2 new bone lesions suggested by a bone scan according to PCWG3 criteria; and/or progression of soft tissue lesions suggested by computed tomography (CT) or nuclear magnetic resonance imaging (MRI) according to RECIST v1.1); meeting either or both criteria;
- Persistent luteinizing hormone-releasing hormone (LHRH) analogue castration (medical castration) or prior bilateral orchiectomy (surgical castration); surgical castration should be performed at least 3 months prior to enrollment, and medical castration is required from at least 3 months prior to the first dose and throughout the study for subjects not yet undertake bilateral orchiectomy; • Patients with progression on or intolerance to at least one prior novel hormone therapy (NHT) (e.g., enzalutamide, abiraterone, darolutamide, apalutamide, or rezvilutamide); • Prior therapy with no more than 2 lines of chemotherapy is allowed; • Patients with known previous prostate adenocarcinoma with a documented BRCA1/2 (germline or somatic) mutation should have received poly ADP ribose polymerase (PARP) inhibitor therapy (if available and tolerated);
Patients with metastatic lesions confirmed by CT, MRI, or bone scan imaging within 28 days prior to the first dose.
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.

• Fresh tumor tissue samples (formalin-fixed, paraffin-embedded (FFPE) tumor blocks or FFPE sections) should be provided for retrospective detection of B7H3 expression by the central laboratory using the immunohistochemistry [IHC] method; if fresh tumor tissue samples are not available, FFPE tumor blocks previously archived are acceptable, and fresh FFPE sections should be prepared within 2 weeks.
Eastern cooperative oncology group performance status (ECOG PS) score of 0 or 1.
The function of organs and bone marrow meets the requirements within 7 days prior to the first dose, which is defined as follows:

• Hemoglobin (Hb) ≥ 90 g/L (no blood transfusion or erythropoietin treatment within 14 days prior to the first dose);

• Absolute neutrophil count (ANC) ≥ 1.5×109/L (no treatment with granulocyte colony stimulating factor or granulocyte-macrophage colony stimulating factor within 14 days prior to the first dose);

• Platelet count (PLT) ≥ 100×109/L (no platelet transfusion, thrombopoietin, or interleukin-11 within 14 days prior to the first dose);

• Total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN) in the absence of obvious liver metastasis, or ≤ 3×ULN in the presence of liver metastasis;

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN in the absence of obvious liver metastasis or ≤ 5×ULN in the presence of liver metastasis;

• Serum albumin (ALB) ≥ 30 g/L;

• Creatinine clearance calculated using Cockcroft-Gault formula ≥ 50 mL/min or the creatinine ≤ 1.5×ULN;
- Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5×ULN, except for patients who are on anticoagulant therapy. In this case, a stable anticoagulant regimen should be maintained with APTT and INR controlled within the range deemed appropriate by the investigator.
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.
Expected survival ≥ 6 months.
Be capable of and willing to comply with the visits and procedures stipulated in the study protocol.

Exclusion Criteria

Previously treated with drugs targeting B7H3.
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.
Previously treated with topoisomerase I inhibitors or ADC therapy composed of topoisomerase I inhibitors.
The washout period of the previous anti-tumor therapy is considered insufficient.
Patients received major surgery.
Prior treatment with allogeneic bone marrow transplantation or solid organ transplantation.
Prior treatment with glucocorticoids for more than 28 consecutive days within 28 days prior to the first dose of the investigational drug.
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.
Have pathological long bone fracture, or the risk of pathological long bone fracture.
Have meningeal metastasis or cancerous meningitis.
Have uncontrolled bladder outlet obstruction or urinary incontinence.
Have brain metastasis or spinal cord compression.
Patients with uncontrolled or clinically significant cardiovascular diseases.
Clinically significant complicated pulmonary disorders.
Diagnosed with Gilbert's syndrome.
Accompanying uncontrolled effusion in the third space requiring repeated drainage.
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.
Active serious infection (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] ≥ 3) within 4 weeks prior to the first dose.
Known human immunodeficiency virus (HIV) infection.
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
Diagnosed with the other malignancies that may change the expected survival or affect the response evaluation.
Unresolved toxicity of previous anti-tumor therapy.
History of severe hypersensitivity to inactive ingredients in the drug substance and drug product or other monoclonal antibodies.
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 Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part 1	YL201 for Injection	To evaluate the safety and efficacy of YL201 in patients with mCRPC and to determine the recommended dose of YL201 for the pivotal clinical study (n ≈ 60)； Cohort 1: YL201 2.0 mg/kg iv Q3W ； Cohort 2: YL201 1.6 mg/kg iv Q3W； Cohort 3: YL201 2.4 mg/kg iv Q3W； Cohort 4: YL201 1.2 mg/kg iv D1, D8 Q3W； Cohort 5: YL201 1.0 mg/kg iv D1, D8, Q3W；
Part2	YL201 for Injection	To evaluate the safety and efficacy of YL201 in patients with mCRPC and to determine the recommended dose of YL201 for the pivotal clinical study (n ≈ 40)； Recommended dose and method of administration

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR) by RECIST1.1 and PCWG3 criteria per investigators' review	Approximately within 36 months	defined as percentage of participants with confirmed best overall response of confirmed complete response (CR) or partial response (PR) to treatment
Radiographic progression free survival (rPFS), and rPFS rate at 3/6 months by RECIST1.1 and PCWG3 criteria per investigators' review	Approximately within 36 months	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.
Recommended dose of YL201 for the pivotal clinical trial.	Approximately within 36 months

Secondary Outcome Measures

Name	Time	Method
To evaluate TTPP of YL201 in the treatment of mCRPC	Approximately within 36 months	time to PSA progression
To evaluate TFST of YL201 in the treatment of mCRPC	Approximately within 36 months	time to first subsequent therapy
disease control Rate (DCR) by RECIST1.1 and PCWG3 criteria per investigators' review	Approximately within 36 months	Disease control rate
To evaluate DoR by RECIST1.1 and PCWG3 criteria per investigators' review of YL201 in the treatment of mCRPC	Approximately within 36 months	Duration of rasponse
To evaluate TTR of YL201 in the treatment of mCRPC	Approximately within 36 months	Time to Objective response
To evaluate DpR of YL201 in the treatment of mCRPC	Approximately within 36 months	deepness of response
To evaluate PSA50 response rate and PSA50 response rate at 12 weeks of YL201 in the treatment of mCRPC	Approximately within 36 months	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%.
To evaluate TTPR of YL201 in the treatment of mCRPC	Approximately within 36 months	time to PSA response
To evaluate PDoR of YL201 in the treatment of mCRPC	Approximately within 36 months	PSA duration of response
To evaluate PDpR of YL201 in the treatment of mCRPC	Approximately within 36 months	PSA deepness of response
To evaluate the Cmax of YL201	Approximately within 36 months	Maximum concentration: The highest measured concentration of YL201 in the bloodstream.
To evaluate the Ctrough of YL201	Approximately within 36 months	trough concentration
To evaluate the T1/2 of YL201	Approximately within 36 months	Terminal half-life: defined as the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%
To evaluate rPFS of YL201 in the treatment of mCRPC	Approximately within 36 months	Radiographic Progression Free Survival
To evaluate the E-R relationship of YL201	Approximately within 36 months	exposure-response
To evaluate OS of YL201 in the treatment of mCRPC	Approximately within 36 months	overall survival
Expression of B7H3 in tumor tissue at baseline and the relationship with the efficacy of YL201.	Approximately within 36 months
To evaluate the CL of YL201	Approximately within 36 months	Clearance: defined as the amount of drug removed from the bloodstream by the body per unit of time
To evaluate the Vd of YL201	Approximately within 36 months	volume of distribution
To evaluate the immunogenicity of YL201	Approximately within 36 months
To evaluate time to first symptomatic skeletal event of YL201 in the treatment of mCRPC	Approximately within 36 months	assessed by investigator according to RECIST v1.1 and PCWG3 criteria
Number of participants with AEs, SAEs, and SAEs leading to study treatment interruption or discontinuation.	Approximately within 36 months	adverse event, serious adverse event
To evaluate the AUC of YL201	Approximately within 36 months	the area under curve: AUC is the total amount of YL201 in bloodstream after drug administration

Trial Locations

Locations (24): Peking University First Hospital
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Peking, Beijing, China
Peking University Third Hospital
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Peking, Beijing, China
Hunan Cancer Hospital
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Hunan, Changsha, China
Chongqing University Cancer Hospital
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Chongqing, Chongqing, China
Nantong Tumor Hospital
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Nantong, Jiangsu, China
Liaoning Cancer Hospital
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Shenyang, Liaoning, China
Shandong Tumor Hospital
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Jinan, Shandong, China
The First Affiliated Hospital of China Medical University
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Shenyang, Liaoning, China
Zhongshan Hospital of Fudan University
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Shanghai, Shanghai, China
The First Affiliated Hospital of Zhejiang University School of Medicine
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Hangzhou, Zhejiang, China
Zhejiang Provincial People's Hospital
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Hangzhou, Zhejiang, China
West China Hospital of Sichuan University
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Chengdu, Sichuan, China
Ningbo Yinzhou No.2 Hospital
🇨🇳
Ningbo, Zhejiang, China
Fudan University Shanghai Cancer Center
🇨🇳
Shanghai, China
Anhui Provincial Hospital
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Hefei, Anhui, China
Harbin Medical University Cancer Hospital
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Harbin, Heilongjiang, China
The Second Affiliated Hospital of Anhui Medical University
🇨🇳
Hefei, Anhui, China
The First Affiliated Hospital of Zhengzhou University
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Zhengzhou, Henan, China
Sichuan Provincial People's Hospital
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Chengdu, Sichuan, China
The Second Hospital of Tianjin Medical University
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Tianjin, Tianjin, China
The First Affiliated Hospital of Wenzhou Medical University
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Wenzhou, Zhejiang, China
Sun Yat-Sen University Cancer Center
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Guangzhou, Guangdong, China
Union Hospital of Huazhong University of Science and Technology Tongji Medical College
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Wuhan, Hubei, China
Nanjing Drum Tower hospital
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Nanjing, Jiangsu, China

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

Recruitment & Eligibility

Study & Design

Trial Locations

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