A Pilot Study of a DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- All Cohorts: Number of participants experiencing study drug-related toxicities
研究概览
简要总结
The primary objective of the trial is the safety and tolerability of administering a vaccine targeting the DNAJB1-PRKACA fusion kinase, in combination with nivolumab and ipilimumab in patients with unresectable or metastatic FLC and with non-FLC solid tumors and to assess the T-cell response.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
Cohort A: Patients with FLC cancer with no prior checkpoint inhibitor treatment. Cohort B: Patients with FLC cancer with prior checkpoint inhibitor treatment. Cohort C: Patients with non-FLC cancer (solid tumors) with prior checkpoint inhibitor treatment eligible.
干预措施: DNAJB1-PRKACA peptide vaccine (Drug)
DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
Cohort A: Patients with FLC cancer with no prior checkpoint inhibitor treatment. Cohort B: Patients with FLC cancer with prior checkpoint inhibitor treatment. Cohort C: Patients with non-FLC cancer (solid tumors) with prior checkpoint inhibitor treatment eligible.
干预措施: Nivolumab (Drug)
DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
Cohort A: Patients with FLC cancer with no prior checkpoint inhibitor treatment. Cohort B: Patients with FLC cancer with prior checkpoint inhibitor treatment. Cohort C: Patients with non-FLC cancer (solid tumors) with prior checkpoint inhibitor treatment eligible.
干预措施: Ipilimumab (Drug)
R- Enrollment: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
Re-enrolling patients: Patients previously treated with the vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with nivolumab and ipilimumab, who, in the opinion of the principal investigator, had clinical or radiological benefits. Re-enrolling patients who come off treatment ≤ 12 months from last dose may resume therapy at the study timepoint that they stopped study therapy. Patients who came off study therapy > 12 months of last dose (i.e. to pursue alternative therapies (for example, surgical debulking), or after completion of the 2 years of study therapy), may restart study therapy at C1D1. In both cases, if the investigator assesses a drug-related toxicity to be related to anti-CTLA4 (ie. not anti-PD(L)1) therapy, patients can be enrolled in the study with nivolumab plus FLC peptide vaccine only.
干预措施: DNAJB1-PRKACA peptide vaccine (Drug)
R- Enrollment: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
Re-enrolling patients: Patients previously treated with the vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with nivolumab and ipilimumab, who, in the opinion of the principal investigator, had clinical or radiological benefits. Re-enrolling patients who come off treatment ≤ 12 months from last dose may resume therapy at the study timepoint that they stopped study therapy. Patients who came off study therapy > 12 months of last dose (i.e. to pursue alternative therapies (for example, surgical debulking), or after completion of the 2 years of study therapy), may restart study therapy at C1D1. In both cases, if the investigator assesses a drug-related toxicity to be related to anti-CTLA4 (ie. not anti-PD(L)1) therapy, patients can be enrolled in the study with nivolumab plus FLC peptide vaccine only.
干预措施: Nivolumab (Drug)
R- Enrollment: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
Re-enrolling patients: Patients previously treated with the vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with nivolumab and ipilimumab, who, in the opinion of the principal investigator, had clinical or radiological benefits. Re-enrolling patients who come off treatment ≤ 12 months from last dose may resume therapy at the study timepoint that they stopped study therapy. Patients who came off study therapy > 12 months of last dose (i.e. to pursue alternative therapies (for example, surgical debulking), or after completion of the 2 years of study therapy), may restart study therapy at C1D1. In both cases, if the investigator assesses a drug-related toxicity to be related to anti-CTLA4 (ie. not anti-PD(L)1) therapy, patients can be enrolled in the study with nivolumab plus FLC peptide vaccine only.
干预措施: Ipilimumab (Drug)
结局指标
主要结局
All Cohorts: Number of participants experiencing study drug-related toxicities
时间窗: 4 years
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
All Cohorts: Fold change in interferon-producing DNAJB1-PRKACA-specific CD4 and CD8 T cells at 10 weeks
时间窗: Baseline and 10 weeks
Evaluated by the fold change in interferon-producing DNAJB1-PRKACA-specific CD8 cells after vaccination at 10 weeks compare to pre-vaccination baseline.
Cohort A only: Progression-free survival (PFS)
时间窗: 6 months
PFS at 6 months, will be estimated as the proportion of subjects who remain alive and free of disease progression at 6 months from the start of treatment. Disease progression will be determined using RECIST 1.1 criteria. The proportion of subjects achieving PFS at 6 months will be estimated using the Kaplan-Meier method, and the corresponding 95% confidence interval will be reported.
次要结局
- Overall survival (OS)(4 years)
- Disease control rate (DCR)(4 years)
- Progression-free survival (PFS)(4 years)
- Objective response rate (ORR)(4 years)
- Duration of response (DoR)(4 years)