Clinical trial NCT06107686: A Study of YL202 in Selected Patients with Advanced Solid Tumors
Official title: A Multicenter, Open-Label, Phase II Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of YL202 in Selected Patients with Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: NSCLC
Breast Cancer
HNSCC
Locally Advanced or Metastatic Solid Tumors
Keywords: Antibody-drug conjugate
Lead sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-10-30
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a multicenter, open-label, phase II study of YL202 in China to evaluate the efficacy, safety, and PK characteristics of YL202 in the following selected patients with advanced solid tumors.

Detailed description: This study is a multicenter, open-label, phase II study of YL202 in China to evaluate the efficacy, safety, and PK characteristics of YL202 in the advanced NSCLC/BC/HNSCC/colorectal cancer/HER2-positive gastric cancer/cervical cancer/ovarian cancer and etc.

Eligibility criteria: Inclusion Criteria:

1. Subjects who are aware of relevant trial information before the start of the trial, and voluntarily sign and date on the informed consent form (ICF).
2. Subjects aged from 18-75 (inclusive) years.
3. Histologically or cytologically confirmed at diagnosis of NSCLC/BC/HNSCC/other locally advanced or metastatic solid tumors including but not limited to colorectal cancer, HER2-positive gastric cancer, cervical cancer, ovarian cancer, etc..
4. At least one extracranial measurable lesion according to RECIST 1.1.
5. Archived or fresh tumor tissue samples can be provided.
6. With 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 before the first dose.
8. Female subjects of childbearing potential 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 product. Male subjects 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 product.
9. With expected survival ≥ 3 months.
10. Be capable of and willing to comply with the visits and procedures stipulated in the study protocol.

Exclusion Criteria:

1. With prior drug therapy targeting HER3 (including antibodies, antibody-drug conjugates \[ADCs\]), chimeric antigen receptor T-cell immunotherapy (CAR-T), and other drugs).
2. Previously intolerant to topoisomerase I inhibitors or ADC therapy composed of topoisomerase I inhibitors.
3. Are participating in another clinical study, unless it is an observational (non-interventional) clinical study or in the follow-up period of an interventional study.
4. The washout period from the previous anti-tumor therapy is insufficient before the first dose of the investigational product.
5. Patients who have received major surgery (excluding diagnostic surgery) within 4 weeks before the first dose of the investigational product or those who are expected to receive major surgery during the study.
6. Prior treatment with allogeneic bone marrow transplantation or solid organ transplantation.
7. Prior treatment with systemic steroids (prednisone \> 10 mg/day or equivalent) or other immunosuppressive treatment within 2 weeks before the first dose of the investigational product.
8. Patients who have received any live vaccine within 4 weeks before the first dose of the investigational product or those who plan to receive live vaccine during the study period.
9. With meningeal metastasis or cancerous meningitis.
10. With brain metastasis or spinal cord compression.
11. Patients with uncontrolled or clinically significant cardiovascular diseases.
12. Clinically significant complicated pulmonary disorders.
13. Patients diagnosed with Gilbert syndrome.
14. Those with uncontrolled effusion in the third space requiring repeated drainage.
15. With a medical history of gastrointestinal perforation and/or fistula within 6 months before the first dose, or with active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal diseases that may lead to hemorrhage or perforation according to the investigator.
16. With serious infection before the first dose.
17. With known human immunodeficiency virus (HIV) infection.
18. With active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
19. With a medical history of any other primary malignancies within 5 years before the first dose of the investigational product.
20. Unrelieved toxicity of previous anti-tumor therapy.
21. With a history of severe hypersensitivity to inactive ingredients in the raw materials and drug product or other monoclonal antibodies.
22. Lactating women, or women who are confirmed pregnant via a pregnancy test within 3 days before the first dose.
23. With any diseases, medical conditions, organ system dysfunction, or social conditions that may interfere with the ability of subjects to sign the ICF, adversely affect the ability of subjects 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: ORR assessed according to RECIST v1.1
timeFrame: By the end of trial date, approximately within 36 months
measure: Determination of the recommended dose of YL202 in the pivotal clinical study
timeFrame: By the end of trial date, approximately within 36 months
Secondary outcomes:
measure: Progression-free survival (PFS) assessed according to RECIST v1.1
timeFrame: approximately within 36 months
measure: Clinical benefit rate (CBR) assessed according to RECIST v1.1
timeFrame: approximately within 36 months
measure: depth of response (DpR) assessed according to RECIST v1.1
timeFrame: Approximately within 36 months
measure: disease control rate (DCR) assessed according to RECIST v1.1
timeFrame: Approximately within 36 months
measure: duration of response (DOR) assessed according to RECIST v1.1
timeFrame: Approximately within 36 months
measure: time to response (TTR) assessed according to RECIST v1.1
timeFrame: Approximately within 36 months
measure: Evaluate the overall survival (OS)
timeFrame: Approximately within 36 months
measure: Adverse event (AE), described in terms of type, frequency, severity, time, and relationship with study treatment
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter AUC
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Cmax
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Ctrough
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter CL
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Vd
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter t1/2
timeFrame: Approximately within 36 months
measure: Incidence of anti-YL202 antibody
timeFrame: approximately within 36 months
measure: Establish a POP PK model for exposure-response relationship analysis
timeFrame: approximately within 36 months
measure: Evaluate the relatonship between different levels of HER3 expression and the sum of CR rate, PR rate and SD rate
timeFrame: approximately within 36 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Tumour Hospital
state: Anhui
city: Hefei
country: China
facility: The first affiliated hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tsinghua Chang Gung Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Chongqing
country: China
facility: Chinese First Affiliated Hospital of Army Medical University of the People's Liberation Army
state: Chongqing
city: Chongqing
country: China
facility: Chongqing University Affiliated Tumor Hospital
state: Chongqing
city: Chongqing
country: China
facility: The first affiliated hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: Xinqiao Hospital of AMU
state: Chongqing
city: Chongqing
country: China
facility: Xinqiao Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Tumor Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Meizhou
country: China
facility: Meizhou People's Hospital
state: Guangdong
city: Shantou
country: China
facility: Shantou University Medical College Tumour Hospital
state: Guangdong
city: Guilin
country: China
facility: Guilin Medical College Second Affiliated Hospital
state: Guangxi
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumour Hospital
state: Guangxi
city: Nanning
country: China
facility: The People's Hospital of Guangxi
state: Guangxi
city: Harbin
country: China
facility: Harbin Medical university cancer hospital
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital Of Henan University&Technology
state: Henan
city: Nanyang
country: China
facility: The First Affiliated Hospital of Nanyang Medical College
state: Henan
city: Xinxiang
country: China
facility: Xinxiang Medical University No.1 Affiliated Hospital
state: Henan
city: Zhengzhou
country: China
facility: He'nan Cancer Hospital South Gate
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial Chest Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Jingzhou
country: China
facility: The First Peoples Hospital of Jingzhou
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College HuaZhong University of Science Technology
state: Hubei
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College,Huazhong University of Science and Technology
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: Hu'nan Province Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya hospital Central South University
state: Hunan
city: Yueyang
country: China
facility: The Third People's Hospital of Hunan Province
state: Hunan
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou medical University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan Medical University
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The Affiliated Hospital of NanChang University
state: Jiangxi
city: Nanchang
country: China
facility: The Third Hospital of Nanchang
state: Jiangxi
city: Changchun
country: China
facility: Jilin Provincial Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: The second Hospital of Dalian Medical University
state: Liaoning
city: Fushun
country: China
facility: Fukuang General Hospital of Liaoning Health Industry Group
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University Physical Examination Center
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital Affiliated to Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Public Health Clinical Center
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Shanghai
country: China
facility: The Affiliated Huashan Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: The No.10 Peoples Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Province Cancer Hospital
state: Shanxi
city: Xian
country: China
facility: The First Affiliated Hospital Of Xi'an JiaoTong University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
city: Chengdu
country: China
facility: SiChuan Cancer Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital,Sichuan Universtiy
state: Sichuan
city: Urumqi
country: China
facility: The Affiliated Cancer Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Tumor Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University school of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: ZheJiang Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Province People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Province People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang University Medical College Affiliated No.1 Hospital
state: Zhejiang
city: Jinhua
country: China
facility: Yiwu Central Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang
state: Zhejiang
Study officials:
References: