A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer naïve to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06A.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 46
- 主要终点
- Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase
研究概览
简要总结
This is a phase I/II multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of investigational agents with pembrolizumab, plus chemotherapy or lenvatinib, for the treatment of participants with advanced esophageal cancer who have failed 1 prior line of therapy and have not been previously exposed to programmed cell death 1 protein (PD-1)/ programmed cell death ligand 1 (PD-L1) based treatment.
With protocol amendment 5 (effective: 17-November-2023), enrollment in study arms "Pembrolizumab plus MK-4830 plus Chemotherapy" and "Pembrolizumab plus MK-4830 plus lenvatinib" is discontinued.
详细描述
The master protocol is MK-3475-U06.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable ESCC
- •Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy.
- •Has an evaluable baseline tumor sample (newly obtained or archival) for analysis
- •Has adequately controlled blood pressure (BP) with or without antihypertensive medications
- •Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible
排除标准
- •Direct invasion into adjacent organs such as the aorta or trachea
- •Has experienced weight loss >10% over approximately 2 months prior to first dose of study therapy
- •Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative therapy
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •History of human immunodeficiency virus (HIV) infection
- •History of Hepatitis B or known active Hepatitis C virus infection
- •History of allogenic tissue/solid organ transplant
- •Clinically significant cardiovascular disease within 12 months from first dose of study intervention
- •Participants with known gastrointestinal (GI) malabsorption or any other condition that may affect the absorption of lenvatinib
- •Has risk for significant GI bleeding, such as:
- •Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization
- •Has significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization
研究组 & 干预措施
Pembrolizumab plus chemotherapy
Participants will receive pembrolizumab intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab plus chemotherapy
Participants will receive pembrolizumab intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Irinotecan (Drug)
Pembrolizumab plus chemotherapy
Participants will receive pembrolizumab intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Paclitaxel (Drug)
Coformulation Favezelimab/Pembrolizumab plus Chemotherapy
Participants will receive coformulation of favezelimab/pembrolizumab administered intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Coformulation favezelimab/pembrolizumab (Biological)
Coformulation Favezelimab/Pembrolizumab plus Chemotherapy
Participants will receive coformulation of favezelimab/pembrolizumab administered intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Irinotecan (Drug)
Coformulation Favezelimab/Pembrolizumab plus Chemotherapy
Participants will receive coformulation of favezelimab/pembrolizumab administered intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Paclitaxel (Drug)
Pembrolizumab plus MK-4830 plus Chemotherapy
Participants will receive pembrolizumab intravenously plus MK-4830 plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab plus MK-4830 plus Chemotherapy
Participants will receive pembrolizumab intravenously plus MK-4830 plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: MK-4830 (Biological)
Pembrolizumab plus MK-4830 plus Chemotherapy
Participants will receive pembrolizumab intravenously plus MK-4830 plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Irinotecan (Drug)
Pembrolizumab plus MK-4830 plus Chemotherapy
Participants will receive pembrolizumab intravenously plus MK-4830 plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Paclitaxel (Drug)
Pembrolizumab plus MK-4830 plus lenvatinib
Participants will receive pembrolizumab intravenously plus MK-4830 plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab plus MK-4830 plus lenvatinib
Participants will receive pembrolizumab intravenously plus MK-4830 plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: MK-4830 (Biological)
Pembrolizumab plus MK-4830 plus lenvatinib
Participants will receive pembrolizumab intravenously plus MK-4830 plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase
时间窗: Up to approximately 3 weeks
A DLT is defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle.
Number of Participants Experiencing an Adverse Event (AE) During Safety Lead-in Phase
时间窗: Up to approximately 3 Weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase
时间窗: Up to approximately 3 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Objective Response Rate (ORR)
时间窗: Up to approximately 40 months
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
次要结局
- Progression-Free Survival (PFS)(Up to approximately 40 months)
- Duration of Response (DOR)(Up to approximately 40 months)
- Overall Survival (OS)(Up to approximately 40 months)
- Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase(Up to approximately 40 months)
- Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase(Up to approximately 104 weeks)