A Phase 1/2, Safety Lead-in and Dose Expansion, Open-label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Activity of Ivosidenib in Combination With Nivolumab and Ipilimumab in Previously Treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 5
- 主要终点
- Safety Lead-In Phase: Number of Dose Limiting Toxicities (DLTs) Associated With Study Drug Regimen, During the First 2 Cycles of Treatment
研究概览
简要总结
This is a Phase 1/2 study evaluating the safety, tolerability, and activity of ivosidenib in combination with immunotherapy in participants with nonresectable or metastatic cholangiocarcinoma. The study includes two phases: the safety lead-in phase to determine the recommended combination dose (RCD) of ivosidenib in combination with immunotherapy and the dose expansion phase to assess the efficacy of ivosidenib in combination with immunotherapy. Study treatment will be administered until participant experiences unacceptable toxicity, disease progression, or other discontinuation criteria are met.
This study was terminated by the sponsor before the expansion phase began and therefore participants were only involved in the safety lead-in phase.
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
- •Male of female participant age ≥ 18 years old
- •Have documented IDH1 gene-mutated disease based on local testing procedure (R132C/L/G/H/S mutations variants tested)
- •Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
- •Has a histopathological diagnosis consistent with nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies
- •Participants must have at least one measurable lesion as defined by RECIST Version 1.
- •Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or if within the field but has shown ≥ 20% growth in size post-treatment assessment.
排除标准
- •Received prior treatment with an IDH inhibitor or prior treatment with an immune checkpoint inhibitor other than anti-PD1/L1
- •Have active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment
- •Participants who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 1 non-hematologic toxicity, according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, prior to the first IMP administration. Residual Grade ≤ 2 toxicity from chemotherapy (e.g., alopecia, neuropathy) may be allowed.
- •Have known symptomatic brain metastases requiring steroids. Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and have radiographically stable disease for at least 3 months prior to study entry. Note: Up to 10 mg per day of prednisone equivalent will be allowed.
研究组 & 干预措施
Safety Lead-In Phase - Ivosidenib 250mg
干预措施: Ivosidenib (Drug)
Safety Lead-In Phase - Ivosidenib 500mg
干预措施: Nivolumab (Drug)
Safety Lead-In Phase - Ivosidenib 250mg
干预措施: Nivolumab (Drug)
Safety Lead-In Phase - Ivosidenib 500mg
干预措施: Ivosidenib (Drug)
Safety Lead-In Phase - Ivosidenib 500mg
干预措施: Ipilimumab (Drug)
Safety Lead-In Phase - Ivosidenib 250mg
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Safety Lead-In Phase: Number of Dose Limiting Toxicities (DLTs) Associated With Study Drug Regimen, During the First 2 Cycles of Treatment
时间窗: Through the end of Cycle 2, day 42 (Cycle 1 and 2 are each 21 days)
Occurring during the safety lead-in phase
Safety Lead-In Phase: Number of Adverse Events (AEs)
时间窗: Through study termination (approximately 1 year)
Occurring during the safety lead-in phase
Safety Lead-In Phase: Number of Participants With Adverse Events of Special Interests (AESIs)
时间窗: Through study termination (approximately 1 year)
Occurring during the safety lead-in phase
Safety Lead-In Phase: Number of Serious Adverse Events (SAEs)
时间窗: Through study termination (approximately 1 year)
Occurring during the safety lead-in phase
次要结局
- Safety Lead-In Phase: Area Under the Concentration-vs-time Curve (AUC) From 0 to Time of Last Measurable Concentration (AUC0-t)(Up to 3 years)
- Safety Lead-In Phase: Plasma 2-hydroxyglutarate (2-HG) Concentration(up to 3 years)
- Safety Lead-In Phase: AUC Over 1 Dosing Interval at Steady State (AUCtau,ss)(Up to 3 years)
- Safety Lead-In Phase: Time to Maximum Concentration (Tmax)(Up to 3 years)
- Safety Lead-In Phase: Maximum Concentration (Cmax)(Up to 3 years)
- Safety Lead-In Phase: Trough Concentration (Ctrough)(Up to 3 years)
- Safety Lead-In Phase: Apparent Volume of Distribution (Vd/F)(Up to 3 years)
- Safety Lead-In Phase: Apparent Clearance (CL/F)(Up to 3 years)