Clinical trial NCT06241846: A Phase II Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Patients With mCRPC
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer (mCRPC)
Lead sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-02-05
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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:

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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 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);
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.

   • 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.
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, 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.
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.

Primary outcomes:
measure: Objective response rate (ORR) by RECIST1.1 and PCWG3 criteria per investigators' review
timeFrame: Approximately within 36 months
measure: Radiographic progression free survival (rPFS), and rPFS rate at 3/6 months by RECIST1.1 and PCWG3 criteria per investigators' review
timeFrame: Approximately within 36 months
measure: Recommended dose of YL201 for the pivotal clinical trial.
timeFrame: Approximately within 36 months
Secondary outcomes:
measure: disease control Rate (DCR) by RECIST1.1 and PCWG3 criteria per investigators' review
timeFrame: Approximately within 36 months
measure: To evaluate DoR by RECIST1.1 and PCWG3 criteria per investigators' review of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate TTR of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate DpR of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate PSA50 response rate and PSA50 response rate at 12 weeks of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate TTPR of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate PDoR of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate PDpR of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate TTPP of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate TFST of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate rPFS of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate OS of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: To evaluate time to first symptomatic skeletal event of YL201 in the treatment of mCRPC
timeFrame: Approximately within 36 months
measure: Expression of B7H3 in tumor tissue at baseline and the relationship with the efficacy of YL201.
timeFrame: Approximately within 36 months
measure: Number of participants with AEs, SAEs, and SAEs leading to study treatment interruption or discontinuation.
timeFrame: Approximately within 36 months
measure: To evaluate the AUC of YL201
timeFrame: Approximately within 36 months
measure: To evaluate the Cmax of YL201
timeFrame: Approximately within 36 months
measure: To evaluate the Ctrough of YL201
timeFrame: Approximately within 36 months
measure: To evaluate the CL of YL201
timeFrame: Approximately within 36 months
measure: To evaluate the Vd of YL201
timeFrame: Approximately within 36 months
measure: To evaluate the T1/2 of YL201
timeFrame: Approximately within 36 months
measure: To evaluate the E-R relationship of YL201
timeFrame: Approximately within 36 months
measure: To evaluate the immunogenicity of YL201
timeFrame: Approximately within 36 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Peking
country: China
facility: Peking University First Hospital
state: Beijing
city: Peking
country: China
facility: Peking University Third Hospital
state: Beijing
city: Hunan
country: China
facility: Hunan Cancer Hospital
state: Changsha
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital of Huazhong University of Science and Technology Tongji Medical College
state: Hubei
city: Nanjing
country: China
facility: Nanjing Drum Tower hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Shenyang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Tumor Hospital
state: Shandong
city: Shanghai
country: China
facility: Zhongshan Hospital of Fudan University
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: The Second Hospital of Tianjin Medical University
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Yinzhou No.2 Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
References: