A Multicenter, Open-Label, Phase 1/2 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 in Patients With Selected Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 990
- 试验地点
- 52
- 主要终点
- Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Archived or fresh tumor tissue samples can be provided.
- •Eastern Cooperative Oncology Group - performance scale (ECOG PS) score of 0 or
- •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.
排除标准
- •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.
研究组 & 干预措施
Phase 1 dose expansion stage
Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle; and at dose levels of 1.0 mg/kg and 1.2 mg/kg administered on Days 1 and 8 of each Q3W treatment cycle.
干预措施: YL201 for Injection (Drug)
Phase 2 stage with expanded sample size
Patients will be treated with YL201 intravenous (IV) infusion at PR2D once every 3 weeks (Q3W) as a cycle; and at dose levels of 1.0 mg/kg and 1.2 mg/kg administered on Days 1 and 8 of each Q3W treatment cycle.
干预措施: YL201 for Injection (Drug)
结局指标
主要结局
Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer
时间窗: Time Frame: Approximately within 36 months
PSA response rate: defined as the proportion of patients who achieved a ≥50% decrease in PSA from baseline
Evaluate the AEs as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment
时间窗: By the global end of trial date, approximately within 36 months
Evaluate the objective response rate (ORR) for patients with solid tumors which assessed using RECIST version 1.1
时间窗: Time Frame: Approximately within 36 months
ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).
次要结局
- Characterize the PK parameter AUC(Approximately within 36 months)
- Characterize the PK parameter Vd(Approximately within 36 months)
- Characterize the PK parameter t1/2(Approximately within 36 months)
- Characterize the PK parameter CL(Approximately within 36 months)
- Evaluate the time to response (TTR) for patients assessed using RECIST version 1.1(Approximately within 36 months)
- Evaluate the overall survival (OS) for patients(Approximately within 36 months)
- Evaluate the duration of response (DoR) for patients assessed using RECIST version 1.1(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.)
- Evaluate the time to PSA progression (TTPP) for patients with prostate cancer(Approximately within 36 months)
- Characterize the PK parameter Ctrough(Approximately within 36 months)
- Assess the incidence of anti-YL201 antibodies(Approximately within 36 months)
- Evaluate the progression-free survival (PFS) for patients assessed using RECIST version 1.1(Approximately within 36 months)
- Evaluate the best PSA response for patients with prostate cancer(Approximately within 36 months)
- Characterize the PK parameter Cmax(Approximately within 36 months)
- Evaluate the disease control rate (DCR) for patients assessed using RECIST version 1.1(DCR: defined as the proportion of patients who achieved a best overall response of CR, PR or stable disease (SD).)
- Evaluate the radiographic progression-free survival (rPFS) for patients with prostate cancer(Approximately within 36 months)
- Evaluate the PSA duration of response (PDoR) for patients with prostate cancer(Approximately within 36 months)