A Phase I, Two-arm, Open-label, Single-center, Dose-escalation Study to Evaluate the Safety, Tolerability and Recommended Dose and Delivery Mode of the Pan-immunotherapy in Subjects With Unresectable/ Metastatic Solid Tumors or Lymphomas
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of subjects with specific Manganese-related adverse events
研究概览
简要总结
Identification of T cell inhibitory signals, including PD-1/PD-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. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This study is a first-in-man, Phase I, 3 + 3 dose escalation study of a combined regimen of Manganese and anti-PD-1 antibody with or without chemotherapies in subjects with unresectable/ metastatic solid tumors or lymphomas. This study is designed to assess the safety, tolerability, pharmacokinetic profile (PK profile), mode of delivery and Recommended Phase 2 Dose (RP2D) of this regimen.
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 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 or lymphomas.
- •≥ 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 frontline 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.
- •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.
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.
- •T cell lymphomas or leukemia.
- •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
Dose-Escalation, intranasally
With a standard 3+3 dose escalation design, the enrollment will proceed until the maximum tolerated dose (MTD) has been defined or the highest dose level has been reached.
干预措施: Manganese Chloride (Drug)
Dose-Escalation, intranasally
With a standard 3+3 dose escalation design, the enrollment will proceed until the maximum tolerated dose (MTD) has been defined or the highest dose level has been reached.
干预措施: Anti-PD-1 antibody (Drug)
Dose-Escalation, intranasally
With a standard 3+3 dose escalation design, the enrollment will proceed until the maximum tolerated dose (MTD) has been defined or the highest dose level has been reached.
干预措施: Systemic therapy (Combination Product)
Dose-Escalation, inhalation
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: Manganese Chloride (Drug)
Dose-Escalation, inhalation
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-PD-1 antibody (Drug)
Dose-Escalation, inhalation
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: Systemic therapy (Combination Product)
结局指标
主要结局
Number of subjects with specific Manganese-related adverse events
时间窗: Approximately 6 months
Manganese-related AEs were considered to be that start or worsen after administration Manganese administration，improve after withdrawal, and even occur again after re-administration.
Number of Subjects with treatment-related adverse events (AEs)
时间窗: Approximately 6 months
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.
次要结局
- Preliminary efficacy evaluation(Approximately 6 months)
- The q3w pharmacokinetic profile of Manganese(Approximately 3 months)
- Number of participants with laboratory test abnormalities(Approximately 3 months)
研究者
Han weidong
Principal Investigator
Chinese PLA General Hospital