A Phase 1/2, Open-Label, Dose-Escalation, Safety, Tolerability, and Efficacy Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies (ECHO-208)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 5
- 主要终点
- Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability, and efficacy of epacadostat when given in combination with nivolumab and ipilimumab, and in combination with nivolumab and lirilumab, in participant with advanced or metastatic malignancies.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •During Phase 1, participant with locally advanced or metastatic solid tumors with disease progression on or after treatment with available therapies, or who are intolerant to treatment, or who refuse standard treatment.
- •During Phase 2, participant with advanced cancer who have received at least one prior therapy or are treatment naive, depending on the specified tumor type.
- •Presence of measurable disease per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Expected survival of ≥ 12 weeks.
排除标准
- •Laboratory and medical history parameters not within the Protocol-defined range.
- •Receipt of anticancer medications or investigational drugs within Protocol-defined time frames.
- •Previous radiotherapy within 7 days of Cycle 1 Day
- •Known active central nervous system metastases and/or carcinomatous meningitis.
- •Prior treatment with any immune checkpoint inhibitor and/or an IDO inhibitor.
- •Active infection requiring systemic therapy.
- •Any active or inactive autoimmune disease or syndrome
研究组 & 干预措施
Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Epacadostat (Drug)
Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Nivolumab (Drug)
Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Ipilimumab (Drug)
Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Epacadostat (Drug)
Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Nivolumab (Drug)
Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Ipilimumab (Drug)
Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Epacadostat (Drug)
Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Nivolumab (Drug)
Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Lirilumab (Drug)
Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Epacadostat (Drug)
Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Nivolumab (Drug)
Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID
Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.
干预措施: Lirilumab (Drug)
Phase 2: Dose Expansion: Treatment Group A: Cohort A1
Participants with unresectable or metastatic melanoma (MEL) were planned to be included in this cohort, who did not receive prior systemic therapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.
干预措施: Epacadostat (Drug)
Phase 2: Dose Expansion: Treatment Group A: Cohort A1
Participants with unresectable or metastatic melanoma (MEL) were planned to be included in this cohort, who did not receive prior systemic therapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.
干预措施: Nivolumab (Drug)
Phase 2: Dose Expansion: Treatment Group A: Cohort A1
Participants with unresectable or metastatic melanoma (MEL) were planned to be included in this cohort, who did not receive prior systemic therapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.
干预措施: Ipilimumab (Drug)
Phase 2: Dose Expansion: Treatment Group A: Cohort A2
Participants with advanced or metastatic non-small cell lung cancer (NSCLC) were planned to be included in this cohort, who have received no more than 1 prior line of platinum-based chemotherapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.
干预措施: Epacadostat (Drug)
Phase 2: Dose Expansion: Treatment Group A: Cohort A2
Participants with advanced or metastatic non-small cell lung cancer (NSCLC) were planned to be included in this cohort, who have received no more than 1 prior line of platinum-based chemotherapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.
干预措施: Nivolumab (Drug)
Phase 2: Dose Expansion: Treatment Group A: Cohort A2
Participants with advanced or metastatic non-small cell lung cancer (NSCLC) were planned to be included in this cohort, who have received no more than 1 prior line of platinum-based chemotherapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.
干预措施: Ipilimumab (Drug)
Phase 2: Dose Expansion: Treatment Group B: Cohort B1
Participants with recurrent or metastatic serotonin norepinephrine reuptake inhibitor (SCCHN) were planned to be included in this cohort, who received no more than 1 prior line of platinum-based chemotherapy for recurrent or metastatic disease to receive epacadostat in combination with nivolumab and lirilumab at the MTD/PAD determined from dose escalation phase.
干预措施: Epacadostat (Drug)
Phase 2: Dose Expansion: Treatment Group B: Cohort B1
Participants with recurrent or metastatic serotonin norepinephrine reuptake inhibitor (SCCHN) were planned to be included in this cohort, who received no more than 1 prior line of platinum-based chemotherapy for recurrent or metastatic disease to receive epacadostat in combination with nivolumab and lirilumab at the MTD/PAD determined from dose escalation phase.
干预措施: Nivolumab (Drug)
Phase 2: Dose Expansion: Treatment Group B: Cohort B1
Participants with recurrent or metastatic serotonin norepinephrine reuptake inhibitor (SCCHN) were planned to be included in this cohort, who received no more than 1 prior line of platinum-based chemotherapy for recurrent or metastatic disease to receive epacadostat in combination with nivolumab and lirilumab at the MTD/PAD determined from dose escalation phase.
干预措施: Lirilumab (Drug)
结局指标
主要结局
Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs)
时间窗: Screening through up to 100 days after end of treatment, up to approximately 24 months
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent.
Phase 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
时间窗: Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
ORR was defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
次要结局
- Phase 2: Duration of Response (DOR)(Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24))
- Phase 1: Objective Response Rate (ORR) Based on RECIST v1.1(Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24))
- Phase 1: Duration of Response (DOR)(Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24))
- Phase 1: Progression-free Survival (PFS)(Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24))
- Phase 2: Progression-free Survival (PFS)(Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24))
- Phase 2: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)(Screening through up to 100 days for treatment Group A and 150 days for treatment Group B after end of treatment, up to approximately 24 months)