Phase I/II Study Evaluating Safety and Clinical Efficacy of SHR2150 (TLR7 Agonist) in Combination With Chemotherapy Plus PD-1 or CD47 Antibody in Subjects With Unresectable/ Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Safety of the combined regimen of SHR2150, chemotherapy, PD-1 or CD47 antibody
研究概览
简要总结
This phase I/II trial aims to evaluate safety and efficacy of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody in subjects with unresectable/ metastatic solid tumors. Patients will receive the combined regimen in 3-week treatment cycles. During the Phase 1 dose escalation portion of the trial, three oral doses of SHR2150 will be combined with intravenous administration of chemotherapy and PD-1 or CD47 antibody. In the Phase 2 dose expansion portion, patients will be treated with the Recommended Phase 2 Dose (RP2D) of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody.
详细描述
Identification of T cell inhibitory signals, including PD-1/L1, has prompted the development of a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. However, elimination of cancer by T cells is only one step in the cancer-immunity cycle, which enable providing several therapeutic targets and tailoring of combinations of immune therapies. SHR2150 is a small molecule agonist of toll-like receptors (TLRs) 7 designed to activate antigen-presenting cells and functions as mucosal immunoadjuvants in pre-clinical studies. This study is a first-in-man, Phase I/II, dose escalation/expansion study of a combined regimen of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody in subjects with unresectable/ metastatic solid tumors. This study is designed to assess the safety, tolerability, RP2D and clinical efficacy of this regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have histologically proven unresectable/ metastatic solid tumors.
- •≥ 18 years old.
- •Life expectancy of at least 6 months.
- •Eastern Cooperative Oncology Group performance status 0-
- •Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.
- •Subjects must have received at least two frontlines therapies, except for patients initially diagnosed with local advanced or metastatic pancreatic cancer or cholangiocarcinoma.
- •Subjects must be off prior therapy for at least 4 weeks prior to Day
- •Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. Subjects with Anti-PD-1 antibody are eligible which must be resistance.
- •Adequate organ function.
- •Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
- •Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.
排除标准
- •Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
- •Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
- •Prior organ allograft.
- •Women who are pregnant or breastfeeding.
- •Women with a positive pregnancy test on enrollment or prior to investigational product administration.
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
研究组 & 干预措施
Phase 1 Dose-Escalation
With a standard 3+3 dose escalation design, the enrollment will proceed until the MTD has been defined or the highest dose level has been reached.
干预措施: SHR2150 (Drug)
Phase 1 Dose-Escalation
With a standard 3+3 dose escalation design, the enrollment will proceed until the MTD has been defined or the highest dose level has been reached.
干预措施: Anti-Cancer Agent (Drug)
Phase 2 Dose-Expansion
SHR2150 RP2D will be combined with chemotherapy plus PD-1 or CD47 antibody in 3-week treatment cycles.
干预措施: Anti-Cancer Agent (Drug)
Phase 2 Dose-Expansion
SHR2150 RP2D will be combined with chemotherapy plus PD-1 or CD47 antibody in 3-week treatment cycles.
干预措施: SHR2150 (Drug)
结局指标
主要结局
Safety of the combined regimen of SHR2150, chemotherapy, PD-1 or CD47 antibody
时间窗: 60 days after last dose
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit.
Identify a RP2D of SHR2150 when given in combined regimen
时间窗: 30 days
The Recommended Phase 2 Dose (RP2D) of SHR2150 in the combined regimen will be identified at Phase 1 dose escalation period, and will be used in the phase 2 dose expansion period.
Object response rate (ORR)
时间窗: 24 month
ORR is defined as the proportion of subjects who achieved a partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
次要结局
- Overall survival (OS)(24 months)
- Disease control rate (DCR)(24 months)
- Progression-free survival (PFS)(24 months)
- Duration of Response (DOR)(24 months)
- Time to Response (TTR)(6 months)
研究者
Han weidong
Principal Investigator
Chinese PLA General Hospital