A Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Immunogenicity, and Initial Efficacy of EVM16 Injection as a Single and Combination With Tislelizumab in Subjects With Advanced or Recurrent Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 2
- 主要终点
- safety and tolerability
研究概览
简要总结
The goal of this clinical trial is to learn the side effects, safety and effect of a tumor vaccine (EVM16) alone or in combined with an anti-PD-1 antibody (tislelizumab) . This clinical trial will include solid tumor patients who failed standard treatment.
The main questions to answer are:
Safety of EVM16. Suitable dose of EVM16. Effects of EVM16 combined with tislelizumab.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recurrent or metastatic solid tumors that have been histologically or cytologically pathologically confirmed and are not amenable to radical treatment with surgery or local therapy.
- •Patients with advanced or recurrent solid tumors who have failed prior standard therapy.
- •Expected survival period >6 weeks at the time of informed consent.
- •Adequate organ function
- •Eastern Cooperative Oncology Group (ECOG) Physical Status Score 0 to
- •Is willing to provide archival or fresh tumor tissue samples for EVM16 production.
- •Has adequate treatment washout period prior to first study dose.
- •Has at least one measurable lesion as assessed by the investigator according to RECIST version 1.1 criteria before enrollment.
排除标准
- •Primary central nervous system (CNS) malignancies that are symptomatic, untreated, or in need of curative treatment, or subjects with CNS metastases.
- •Uncontrolled co-morbidities.
- •Cerebrovascular event (stroke, transient ischemic attack, etc.) within 4 months prior to the signing of inform consent form.
- •In screening period male QTcF interval >450 ms; Female QTcF interval >470 ms (calculated by the Fridericia formula).
- •Left ventricular ejection fraction (LVEF) < 50% during the screening period.
- •Diagnosis of immunodeficiency, or history or syndrome of active as well as former autoimmune disease with risk of relapse, or a disease requiring systemic steroid hormone or immunosuppressive drug therapy.
- •Subjects with a history of positive human immunodeficiency virus (HIV) test or acquired immunodeficiency syndrome (AIDS).
- •Co-infection HBV and HCV.
- •Presence of any active infection requiring systemic therapy.
- •Patients who are still on any other investigational medications treatment at the time of screening.
- •Previous treatment with cell therapy, tumor vaccines, cytokines, or growth factors for cancer control.
- •Patients with prior intolerance to tislelizumab resulting in permanent termination of tislelizumab.
- •History or presence of significant lung disease.
研究组 & 干预措施
Dose Escalation Level 1
EVM16 dose level 1 as single and combined therapy with Tislelizumab.
干预措施: EVM16 (Biological)
Dose Escalation Level 1
EVM16 dose level 1 as single and combined therapy with Tislelizumab.
干预措施: Tislelizumab (Drug)
Dose Escalation Level 2
EVM16 dose level 2 as single and combined therapy with Tislelizumab.
干预措施: EVM16 (Biological)
Dose Escalation Level 2
EVM16 dose level 2 as single and combined therapy with Tislelizumab.
干预措施: Tislelizumab (Drug)
Dose Escalation Level 3
EVM16 dose level 3 as single and combined therapy with Tislelizumab.
干预措施: EVM16 (Biological)
Dose Escalation Level 3
EVM16 dose level 3 as single and combined therapy with Tislelizumab.
干预措施: Tislelizumab (Drug)
Dose Expansion
EVM16 RP2D dose in combination with Tislelizumab.
干预措施: EVM16 (Biological)
Dose Expansion
EVM16 RP2D dose in combination with Tislelizumab.
干预措施: Tislelizumab (Drug)
结局指标
主要结局
safety and tolerability
时间窗: From the first study intervention to 90 days after the last study intervention.
The incidence and severity of adverse events (AEs) and serious adverse events (SAEs), the incidence of dose-limiting toxicity (DLT) （only in phase Ia）, and the incidence of AEs of grade 3 or higher were assessed according to the NCI CTCAE v5.0 in the treatment of EVM16 alone as well as EVM16 in combination with Tislelizumab.
RP2D for EVM16
时间窗: During the intervention, up to approximately 1 year.
Based on safety, tolerability, immunogenicity to determine RP2D.
次要结局
- immunogenicity of EVM16(during the intervention, up to 1 year)
- time to remission (TTR) of EVM16 in combination with tislelizumab(From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first.)
- objective response rate (ORR) of EVM16 in combination with tislelizumab(From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first.)
- disease control rate (DCR) of EVM16 in combination with tislelizumab(From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first.)
- duration of disease remission (DOR) of EVM16 in combination with tislelizumab(From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first.)
- PFS of EVM16 in combination with tislelizumab （Only in phase Ib）(From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first)
研究者
Shen Lin
Prof.
Peking University Cancer Hospital & Institute