A Phase 1/2 Study of YH001 in Combination With Envafolimab With or Without Doxorubicin in Patients With Advanced or Metastatic Sarcoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 15
- 试验地点
- 6
- 主要终点
- Phase 1: Determine recommended phase 2 dose of YH001 in combination with Envafolimab
研究概览
简要总结
This is a multicenter, open label, Phase 1/2 study of YH001 initially given in combination with envafolimab, and then given in combination with envafolimab plus doxorubicin in patients with advanced or metastatic sarcoma, followed by Phase 2 cohorts of patients with select histologies of advanced or metastatic sarcoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed advanced or metastatic sarcoma patients without UPS or MFS who are refractory to or intolerant to standard treatments for their disease.
- •Histologically confirmed advanced or metastatic sarcoma patients without UPS or MFS who have not received any immune checkpoint inhibitors or doxorubicin, and with histology for which doxorubicin is considered a reasonable treatment option (for Cohort 1B, 2B and Expanded Cohort 1B and/or 2B)
- •Measurable disease by RECIST 1.1
- •Age ≥ 18 years
- •Adequate organ function
- •Left ventricular ejection fraction (LVEF) as measured by echo or multigated acquisition scan of > 50% (for patients to receive doxorubicin)
- •Willingness and ability to consent for self to participate in study
- •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- •Men who are sterile or agree to use a condom with spermicide .
- •Women of non-child bearing potential due to surgical sterilization or medically-documented ovarian failure confirmed by medical history, or women of child bearing potential who test negative for pregnancy at time of enrollment and agree to use at least 2 acceptable methods of birth control
排除标准
- •Gastrointestinal stromal tumor (GIST) or desmoid tumors
- •Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to enrollment
- •Known allergy to any component of any study drug that the patient would receive if enrolled into this study
- •Prior T-cell or NK-cell therapy
- •Prior pericardial or mediastinal radiation (for patients to receive doxorubicin)
- •Acute coronary syndromes within 6 months of enrollment
- •Women who are pregnant or breast feeding
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study
研究组 & 干预措施
P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.
干预措施: YH001 (Drug)
P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.
干预措施: Envafolimab (Drug)
P1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.
干预措施: YH001 (Drug)
P1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.
干预措施: Envafolimab (Drug)
P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.
干预措施: YH001 (Drug)
P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.
干预措施: Envafolimab (Drug)
P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.
干预措施: Doxorubicin (Drug)
P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.
干预措施: YH001 (Drug)
P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.
干预措施: Envafolimab (Drug)
P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.
干预措施: Doxorubicin (Drug)
P2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks
干预措施: YH001 (Drug)
P2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks
干预措施: Envafolimab (Drug)
P2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks
干预措施: YH001 (Drug)
P2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks
干预措施: Envafolimab (Drug)
P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses
干预措施: Doxorubicin (Drug)
P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses
干预措施: YH001 (Drug)
P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses
干预措施: Envafolimab (Drug)
P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses
干预措施: Doxorubicin (Drug)
P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses
干预措施: YH001 (Drug)
P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK
Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses
干预措施: Envafolimab (Drug)
结局指标
主要结局
Phase 1: Determine recommended phase 2 dose of YH001 in combination with Envafolimab
时间窗: 8 months
Evaluate safety and tolerability and determine the recommended Phase 2 dose (RP2D) of YH001 when given with envafolimab dosed SC every 3 weeks in patients with advanced or metastatic sarcoma who are refractory to or intolerant to other available therapies.
Phase 1: Determine recommended phase 2 dose of YH001 in combination with Envafolimab with Doxorubicin
时间窗: 8 months
Evaluate safety and tolerability and determine RP2D of YH001 in combination with envafolimab dosed SC every 3 weeks and doxorubicin dosed every three weeks in patients with advanced or metastatic sarcoma who have not received doxorubicin and are refractory to or intolerant to other available therapies.
Phase 2: Determine the objective response rate (ORR) of YH001 in combination with Envafolimab and Doxorubicin
时间窗: 18 months
Determine the ORR of envafolimab, YH001 and doxorubicin by RECIST 1.1 by investigator assessment in patients who have not received immune checkpoint inhibitors or doxorubicin with subtypes of advanced or metastatic soft tissue sarcoma.
Phase 2: Determine the objective response rate (ORR) of YH001 in combination with Envafolimab
时间窗: 22 months
Determine the ORR of envafolimab and YH001 by RECIST 1.1 by investigator in patients with subtypes of advanced or metastatic soft tissue sarcoma who have not received immune checkpoint inhibitors.
次要结局
- Phase 2: Determine the Rate of YH001 Immunogenicity(22 months)
- Phase 2: Determine the Rate of Envafolimab Immunogenicity(22 months)
- Phase 1: YH001 concentrations(8 months)
- Phase 1: Envafolimab concentrations(8 months)
- Phase 1: Determine the Rate of YH001 Immunogenicity(8 months)
- Phase 1: Determine the Rate of Envafolimab Immunogenicity(8 months)
- Phase 2: Determine the disease control rate (DCR)(22 months)
- Phase 1: Assessment of antitumor activity(8 months)
- Phase 2: Determine Progression Free Survival (PFS)(22 months)
- Phase 2: Envafolimab concentration(22 months)
- Phase 2: Type Incidence and Severity of Adverse Events(25 months)
- Phase 2: Determine duration of response (DOR)(22 months)
- Phase 2: Determine Overall Survival (OS)(22 months)
- Phase 2: YH001 concentration(22 months)