Clinical trial NCT06057922: A Study YL201 in Patients With Selected Advanced Solid Tumors
Official title: A Multicenter, Open-Label, Phase 1/2 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Patients With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Keywords: Antibody-drug conjugate
Lead sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-09-28
Enrollment: 990
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 is A Multicenter, Open-Label, Phase 1/2 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Patients with Selected Advanced Solid Tumors. The study will include 2 parts: Phase 1 dose expansion stage (Part 1) followed by a Phase 2 stage with expanded sample size (Part 2).

Part 1 will estimate the RP2D in dose expansion cohorts of patients with not linited to non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), nasopharyngeal carcinoma (NPC), esophageal squamous cell carcinoma (ESCC), metastatic castration-resistant prostate cancer (mCRPC), head and neck squamous cell carcinoma (HNSCC), sarcoma, ductal adenocarcinoma of pancreas (PDAC), hepatocellular carcinoma (HCC), biliary tract cancer (BTC), etc..

Part 2 will include patients with selected advanced solid tumor types enrolled at the RP2D to further assess the efficacy and safety of YL201.


Eligibility criteria: Inclusion Criteria:

* Informed of the trial before the start of the trial and voluntarily sign their name and date on the ICF.
* Age ≥18 years old and ≤75 years old
* Histologically or cytologically confirmed at diagnosis of NSCLC/SCLC/NPC/ESCC /mCRPC/HNSCC/Sarcoma/PDAC/HCC/BTC
* At least one extracranial measurable lesion according to RECIST 1.1.
* Archived or fresh tumor tissue samples can be provided.
* Eastern Cooperative Oncology Group - performance scale (ECOG PS) score of 0 or 1.
* Female subjects with fertility must agree to take high-efficiency contraceptive measures from screening to whole study period and within at least 6 months after last administration of investigational drug. Male subjects must agree to take high-efficiency contraceptive measures from screening to whole study period and within at least 6 months after last administration of investigational drug.
* Life expectancy ≥3 months.
* Capable or willing to observe the visits and procedures stipulated in study protocol.

Exclusion Criteria:

* Prior treatment with products targeting B7H3 (including antibodies, antibody-drug conjugate \[ADC\], chimeric antigen receptor T cells \[CAR-T\], and other drugs).
* Prior treatment with topoisomerase 1 inhibitors or ADC based on topoisomerase 1 inhibitors.
* Participation in another clinical trial meanwhile, except observatory (non-interventional) clinical trial or at follow-up period of interventional study.
* Washout period of previous anticancer treatment was insufficient before first administration of investigational drug.
* Major surgery (excluding diagnostic surgery) within 4 weeks before first administration of investigational drug or likely to require major surgery during the study.
* History of allogenic bone marrow transplantation or solid organ transplantation.
* Treatment with systemic steroid (Prednisone \>10 mg/d or equivalent drugs) or other immunosuppressive drugs within 2 weeks before first administration of investigational drug.
* Live vaccination within 4 weeks before first administration of investigational drug or likely to require live vaccine inoculation during the study.
* Evidence of leptomeningeal metastasis or carcinomatous meningitis.
* Evidence of brain metastasis or spinal cord compression.
* Evidence of cardiovascular disease with uncontrolled state or clinical significance.
* Clinically significant concomitant lung disease.
* Diagnosed as Gilbert syndrome.
* Complicated with uncontrolled third-space effusion .
* History of gastrointestinal perforation and/or fistula within 6 months before first administration.
* History of serious infection (Grade ≥3 of NCI CTCAE) before first administration.
* Known as infection with human immunodeficiency virus (HIV).
* Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
* History of any other primary malignant tumor within 5 years before first administration of investigational drug.
* The toxicity of previous anticancer treatment is not resolved.
* History of serious hypersensitive reactions to drug substance, inactive compositions of preparations or other monoclonal antibodies.
* Breastfeeding women. Or women confirmed as pregnant through pregnancy test within 3 days before first administration.
* Any disease, medical state, organ/system dysfunction or social state considered by investigators as possibly interfering the subject's capability for ICF signing, producing adverse influence on the subject's capability for cooperation and study participation or influencing the interpretation of study results. Including but not limited to mental disease or substance/alcohol abuse.

Primary outcomes:
measure: Evaluate the AEs as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment
timeFrame: By the global end of trial date, approximately within 36 months
measure: Evaluate the objective response rate (ORR) for patients with solid tumors which assessed using RECIST version 1.1
timeFrame: Time Frame: Approximately within 36 months
measure: Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer
timeFrame: Time Frame: Approximately within 36 months
Secondary outcomes:
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: Assess the incidence of anti-YL201 antibodies
timeFrame: Approximately within 36 months
measure: Evaluate the disease control rate (DCR) for patients assessed using RECIST version 1.1
timeFrame: DCR: defined as the proportion of patients who achieved a best overall response of CR, PR or stable disease (SD).
measure: Evaluate the duration of response (DoR) for patients assessed using RECIST version 1.1
timeFrame: DoR: defined as the time interval from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of PD. DoR will be assessed for patients with a response (CR or PR) only.
measure: Evaluate the time to response (TTR) for patients assessed using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: Evaluate the progression-free survival (PFS) for patients assessed using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: Evaluate the overall survival (OS) for patients
timeFrame: Approximately within 36 months
measure: Evaluate the radiographic progression-free survival (rPFS) for patients with prostate cancer
timeFrame: Approximately within 36 months
measure: Evaluate the time to PSA progression (TTPP) for patients with prostate cancer
timeFrame: Approximately within 36 months
measure: Evaluate the PSA duration of response (PDoR) for patients with prostate cancer
timeFrame: Approximately within 36 months
measure: Evaluate the best PSA response for patients with prostate cancer
timeFrame: Approximately within 36 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Dongguan
country: China
facility: Dongguan People's Hospital
state: Guangdong
city: Foshan
country: China
facility: The Frist People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Affiliated Cancer Hospital and Institute of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
state: Guangdong
city: Jiangmen
country: China
facility: Jiangmen Central Hospital
state: Guangdong
city: Shaoguan
country: China
facility: Yuebei People's Hospital
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-Sen University
state: Guangdong
city: Guilin
country: China
facility: The Second Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Liuzhou
country: China
facility: Liuzhou People's Hospital
state: Guangxi
city: Liuzhou
country: China
facility: Liuzhou Worker's Hospital
state: Guangxi
city: Nanning
country: China
facility: Affiliated Cancer Hospital of Guangxi Medical University
state: Guangxi
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Haikou
country: China
facility: The First Affiliated Hospital of Hainan Medical University
state: Hainan
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical University
state: Hebei
city: Haerbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
city: Wuxi
country: China
facility: Jiangyin People's Hospital
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 (Jiangxi Second People's Hospital)
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Shenyang
country: China
facility: The Frist Hospital of China Medical University
state: Liaoning
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital and Institute
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Datong
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Xian
country: China
facility: The Second Affiliated Hospital of the Chinese People's Liberation Army Air Force Medical University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
city: Huaxi
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
Study officials:
References: