A Phase I/IIa Trial to Evaluate the Safety and Efficacy of the Combination of the Oncolytic Immunotherapy Pexa-Vec With the PD-1 Receptor Blocking Antibody Nivolumab in the First-line Treatment of Advanced Hepatocellular Carcinoma (HCC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Transgene
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Overall Response Rate (ORR) According to RECIST 1.1.
研究概览
简要总结
This is a study to Evaluate the Safety and Efficacy of the Combination of the Oncolytic Immunotherapy Pexa-Vec With the PD-1 Receptor Blocking Antibody Nivolumab in the First-line Treatment of Advanced Hepatocellular Carcinoma (HCC).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological/cytological diagnosis of primary HCC, excluding cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
- •Advanced stage HCC per EASL-EORTC (European Association for the Study of the Liver-European Organisation for Research and Treatment of Cancer) guidelines, i.e. patients who are not candidates for curative interventions and not candidates for locoregional modalities
- •Patients naïve to systemic therapy for HCC
- •Tumor status (as determined by radiology evaluation): At least one measurable viable tumor in the liver, ≥1 cm longest diameter (LD), using a dynamic imaging technique (arterial phase of triphasic computerized tomography [CT] scan, or dynamic contrast-enhanced magnetic resonance imaging [MRI]), and injectable under imaging-guidance (CT or ultrasound)
- •At least one tumor that has not received prior local-regional treatment, or that has exhibited definitive growth of viable tumor since prior local-regional treatment of HCC undertaken at least 4 weeks prior to enrolment or 3 months prior to enrolment for radioembolization
- •Child-Pugh Class A. Note: paracentesis, albumin infusion or diuretic treatment cannot be used to downgrade Child-Pugh score (e.g., to improve from severe to moderate/mild or from moderate to mild ascites)
- •Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Adequate hematological, hepatic, and renal function
- •Additional inclusion criteria exist
排除标准
- •Histological diagnosis of cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
- •Symptomatic cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months
- •Current or past history of cardiovascular disease (e.g., past history of myocardial infarction, ischemic cardiomyopathy) unless cardiology consultation and clearance has been obtained for study participation
- •History of moderate or severe ascites, bleeding esophageal varices, hepatic encephalopathy or pleural effusions related to liver insufficiency within 6 months of screening; patients with adequately treated esophageal varices are allowed
- •Active, known or suspected significant immunodeficiency due to underlying illness including HIV/AIDS, autoimmune diseases, and/or immune-suppressive medication including high-dose corticosteroids
- •History of severe eczema and/or ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment
- •Any known allergy or reaction to any component of nivolumab formulation or its excipients
- •Additional exclusion criteria exist
研究组 & 干预措施
Pexa-Vec combined with Nivolumab - Phase I
Participants were administered Pexa-Vec (pexastimogene devacirepvec) as 3 bi-weekly intratumoral (IT) injections of 10^9 pfu at day 1 and weeks 2 and 4 and nivolumab intravenously every 2 weeks (from week 2).
干预措施: Pexastimogene Devacirepvec (Pexa Vec) (Biological)
Pexa-Vec combined with Nivolumab - Phase I
Participants were administered Pexa-Vec (pexastimogene devacirepvec) as 3 bi-weekly intratumoral (IT) injections of 10^9 pfu at day 1 and weeks 2 and 4 and nivolumab intravenously every 2 weeks (from week 2).
干预措施: Nivolumab (Drug)
Pexa-Vec combined with Nivolumab - Phase IIa
Participants were administered Pexa-Vec (pexastimogene devacirepvec) as 3 bi-weekly intratumoral (IT) injections of 10^9 pfu at day 1 and weeks 2 and 4 and nivolumab intravenously every 2 weeks (from week 2).
干预措施: Pexastimogene Devacirepvec (Pexa Vec) (Biological)
Pexa-Vec combined with Nivolumab - Phase IIa
Participants were administered Pexa-Vec (pexastimogene devacirepvec) as 3 bi-weekly intratumoral (IT) injections of 10^9 pfu at day 1 and weeks 2 and 4 and nivolumab intravenously every 2 weeks (from week 2).
干预措施: Nivolumab (Drug)
结局指标
主要结局
Overall Response Rate (ORR) According to RECIST 1.1.
时间窗: 6 months from the first study drug administration
Overall Response Rate (ORR): proportion of patients, whose best overall response is either complete response (CR) or partial response (PR), confirmed at least 4 weeks after initial documentation.
Phase I: Number of Participants With Serious Adverse Events (SAEs)
时间窗: 4 weeks from the first study drug administration
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence or effect in a patient, whether or not considered related to the protocol treatment, that at any dose: (i) results in death, (ii) is life-threatening, (iii) requires inpatient's hospitalization or prolongation of existing inpatients´ hospitalization, (iv) results in persistent or significant disability or incapacity, (v) is a congenital anomaly or birth defect, (vi) results in any other medically important condition.
Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: 4 weeks from the first study drug administration
DLTs are occurrence of any following AE related to study drugs occurring during 4 weeks after 1st Pexa-Vec injection: 1. Grade 3-4 non-hematologic toxicity representing a 2-grade increase over baseline, excluding: nausea, vomiting, diarrhea, fever\>40.0°C lasting less than 24h (grade 3), alopecia, grade 3 fatigue\* and grade 3 laboratory/metabolic abnormalities\* (\*returning to grade 2 or less within 72h) 2. Grade ≥ 3 acute immune-related AE involving major organs 3. Grade ≥ 3 injection site reaction 4. AST or ALT ≥ 10xULN unless related to liver metastases progression; AST or ALT doubling concurrent with total bilirubin doubling 5. Any toxicity resulting in treatment delay of 2 or more weeks 6. Grade ≥ 3 or ≥ 2-grade neutropenia increase over baseline lasting \>7 days, neutropenic fever, grade 4 thrombocytopenia (or grade 3 with bleeding) 7. Association of LVEF less than LLN, blood troponin T or I increase above ULN and any ECG abnormality indicating grade 3 cardiac disorder.
次要结局
未报告次要终点