A Phase I/II Open Label Study to Evaluate Safety and the Prophylactic Effect on Recurrence of Anti-PD1 Monotherapy, P1101 Monotherapy, and Sequential Administration of P1101 and Anti-PD1 After Curative Surgery of HBV-related HCC
试验速览
- 阶段
- 1 期
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Phase I portion - Dose-limiting Toxicity
研究概览
简要总结
The main purpose of this trial is to evaluate the safety of the new adjuvant treatment of curative HCC, or the treatment of long-acting interferon P1101 alone, or the use of long-acting interferon P1101 and subsequent treatment of anti-PD1, and any efficacy in reducing the recurrence rate of patients after surgery.
详细描述
secondary end-point: P1101 and anti-PD1 sequential therapy on hepatitis B (especially on HbsAg).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject with HCC who meet the following criteria
- •Subjects diagnosed as having typical HCC on dynamic CT, or dynamic MRI performed within 8 weeks before surgery, or subjects who diagnosed HCC by pathology after surgery resection;
- •Subjects with the primary occurrence HCC ;
- •Subjects with the HCC related to hepatitis B virus (HBV) ;
- •Subject who have undergone surgical liver reaction within 8 weeks prior to study entry.
- •Subjects showing a complete cure shows no findings suggestive of recurrence or remnant. ;
- •Subject who are able to begin treatment with the study drug within 12 weeks after liver surgery resection. ;
- •Subjects confirmed of satisfying the following conditions based on the screening performed at enrollment: Positive for HBsAg/ Undetectable HBV DNA, with or without current anti HBV treatment/ Grade A on Child-Pugh classification;
- •Normal fundoscopic examination by ophthalmologist at screening;
- •ECOG 0 to 1 ;
排除标准
- •Subjects positive for anti-HCV ;
- •Subjects showing vascular invasion of HCC on imaging diagnosis ;
- •Subjects who have uncontrolled hypertension;
- •Subjects with a history of pneumonitis or interstitial lung disease . cardiac arrest . an active infection requiring therapy .;
- •Diabetes mellitus with HbA1c ≥ 7.4% with insulin treatment;
研究组 & 干预措施
P1101 monotherapy
Phase II Study Group II: P1101 arm 450mcg 12 doses
干预措施: P1101 (Ropeginterferon alfa-2b) (Drug)
Sequential administration of P1101 and anti-PD1
Phase I of Study : To determine the safety, tolerability, DLT, and potential phase 2 dose of sequential administration of P1101 and anti-PD1
:Sequential administration 6 doses (450mcg) of P1101 and 3 doses of anti-PD1 (Escalating from 0.3, 0.75, 1.5, 3 mg/kg) for Phase I Study
干预措施: P1101 (Ropeginterferon alfa-2b) (Drug)
Sequential administration of P1101 and anti-PD1
Phase I of Study : To determine the safety, tolerability, DLT, and potential phase 2 dose of sequential administration of P1101 and anti-PD1
:Sequential administration 6 doses (450mcg) of P1101 and 3 doses of anti-PD1 (Escalating from 0.3, 0.75, 1.5, 3 mg/kg) for Phase I Study
干预措施: Nivolumab (Drug)
anti-PD1
Phase II Study Group I: anti-PD1 arm 3mg/kg 3 doses
干预措施: Nivolumab (Drug)
sequential administration of P1101 and anti-PD1
Phase II Study GroupIII:Sequential administration of 6 doses of 450mcg P1101 and followed by 3 doses of anti-PD1 dosage (base on Phase I study result)
干预措施: P1101 (Ropeginterferon alfa-2b) (Drug)
sequential administration of P1101 and anti-PD1
Phase II Study GroupIII:Sequential administration of 6 doses of 450mcg P1101 and followed by 3 doses of anti-PD1 dosage (base on Phase I study result)
干预措施: Nivolumab (Drug)
结局指标
主要结局
Phase I portion - Dose-limiting Toxicity
时间窗: 18 weeks
To determine the potential phase 2 dose of sequestial administration of P1101 and anti-PD1. The MTD is determine by the prior dose level below the dose level at which ≥2/3 or ≥2/6 subjects suffer dose-limiting toxicity (DLT).
Phase II portion - Recurrence-free survival (defined as the time from randomization to HCC recurrence or death from any cause, whichever occured first)
时间窗: 48 weeks
To evaluate safety(assessment of AE, SAE and unanticipated problem) and the recurrence-free survival (defined as the time from randomization to HCC recurrence or death from any cause, whichever occured first) at 48 weeks after randomization of anti-PD 1 monotherapy, P1101 monotherapy, and sequential administration of P1101 and anti-PD 1 therapy arms
次要结局
- Disease-free survival(48 weeks)
- Recurrence-free survival(96 weeks)
- HBsAg level(End of treatment of Anti-PD1 arm is up to 6 weeks; End of treatment of P1101 arm is up to 24 weeks; End of treatment of sequential administration of P1101 and anti-PD1 is up to 18 weeks, 24 weeks and 48 weeks)