A Phase 1/2 Open-label Study to Evaluate the Safety and Efficacy of MK-1200 in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 31
- 主要终点
- Number of Participants who Experience One or More Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of MK-1200 monotherapy in participants with advanced/metastatic gastric/gastroesophageal junction (GEJ) cancer, esophageal cancer, biliary tract cancer, and pancreatic ductal adenocarcinoma who have received, or been intolerant to, all treatments known to confer clinical benefit. Part 1 of the study will be a dose escalation to determine the maximum tolerated dose (MTD). Part 2 will evaluate safety and efficacy of MK-1200 at 2 different doses
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
- •Confirmed advanced (unresectable and/or metastatic) solid tumor: gastric cancer (including gastroesophageal junction cancer), esophageal cancer, biliary tract cancer, or pancreatic ductal adenocarcinoma
- •Participants who experienced Adverse Events (AEs) due to previous anticancer therapies must have recovered to < Grade 1 or baseline
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
- •Hepatitis B surface antigen (HBsAg) positive participants are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load
- •Participants with a history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable
- •Received and progressed on or after 1 or 2 prior lines of therapy
排除标准
- •Active severe digestive disease
- •History of acute myocardial infarction; unstable angina; stroke or transient ischemic attack within 6 months prior to the first dose of study intervention
- •Diabetes or hypertension that cannot be controlled by medication
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before study intervention
- •Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
- •Known additional malignancy that is progressing or has required active treatment within the past 2 years
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Active infection requiring systemic therapy
- •Have not adequately recovered from major surgery or have ongoing surgical complications
研究组 & 干预措施
Part 2: MK-1200 Cohort B
In Part 2, participants in Cohort B will receive Dose 1 of MK-1200 (determined from Part 1) via IV infusion Q2W until any discontinuation criteria are met.
干预措施: MK-1200 (Biological)
Part 2: MK-1200 Cohort B
In Part 2, participants in Cohort B will receive Dose 1 of MK-1200 (determined from Part 1) via IV infusion Q2W until any discontinuation criteria are met.
干预措施: Antiemetic (Drug)
Part 1: MK-1200
In Part 1, participants will receive escalating doses of MK-1200 via intravenous (IV) infusion every 2 weeks (Q2W) until any discontinuation criteria are met.
干预措施: Antiemetic (Drug)
Part 2: MK-1200 Cohort A
In Part 2, participants in Cohort A will receive either Dose 1 or Dose 2 of MK-1200 (determined from Part 1) via IV infusion Q2W until any discontinuation criteria are met.
干预措施: Antiemetic (Drug)
Part 2: MK-1200 Cohort A
In Part 2, participants in Cohort A will receive either Dose 1 or Dose 2 of MK-1200 (determined from Part 1) via IV infusion Q2W until any discontinuation criteria are met.
干预措施: MK-1200 (Biological)
Part 1: MK-1200
In Part 1, participants will receive escalating doses of MK-1200 via intravenous (IV) infusion every 2 weeks (Q2W) until any discontinuation criteria are met.
干预措施: MK-1200 (Biological)
结局指标
主要结局
Number of Participants who Experience One or More Dose-Limiting Toxicities (DLTs)
时间窗: Up to approximately 28 days
The occurrence of any of the following toxicities within 28 days after the first dose of study intervention will be considered a DLT, if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration: * Grade 4 nonhematologic toxicity (not laboratory). Any nonhematologic AE ≥Grade 3 in severity should be considered a DLT, with pre-specified exceptions * Any Grade 3 or Grade 4 laboratory value (hematologic or nonhematologic), with pre-specified exceptions * Febrile neutropenia Grade 3 or Grade 4 as prespecified by the protocol * Prolonged delay (\>2 weeks) in initiating Cycle 2 due to intervention-related toxicity * Any intervention-related toxicity that causes the participant to discontinue intervention during Cycle 1 * Missing \>25% of MK-1200 doses as a result of drug-related AEs during the first cycle * Grade 5 toxicity
Number of Participants who Experience One or More Adverse Events (AEs)
时间窗: Up to approximately 16 months
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported for each arm.
Number of Participants who Discontinue Study Intervention Due to an AE
时间窗: Up to approximately 15 months
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study intervention due to an AE will be reported for each arm.
次要结局
- Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)(Up to approximately 16 months)
- Maximum Concentration (Cmax) of MK-1200(Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 48, 96, 168, and 240 hours postdose; Cycles 2-3 Days 1 and 8: predose and 0.5 hours postdose; Day 1 of Cycles 5 onward (up to 15 months): predose and 0.5 hours postdose. Cycle is 14 days.)
- ORR per RECIST 1.1 as Assessed by Investigator(Up to approximately 16 months)
- Area under the curve (AUC) of MK-1200(Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 48, 96, 168, and 240 hours postdose; Cycles 2-3 Days 1 and 8: predose and 0.5 hours postdose; Day 1 of Cycles 5 onward (up to 15 months): predose and 0.5 hours postdose. Cycle is 14 days.)
- Minimum Concentration (Cmin) of MK-1200(Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 48, 96, 168, and 240 hours postdose; Cycles 2-3 Days 1 and 8: predose and 0.5 hours postdose; Day 1 of Cycles 5 onward (up to 15 months): predose and 0.5 hours postdose. Cycle is 14 days.)
- Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR(Up to approximately 16 months)
- DOR per RECIST 1.1 as Assessed by Investigator(Up to approximately 16 months)
- Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR(Up to approximately 16 months)
- PFS per RECIST 1.1 as Assessed by Investigator(Up to approximately 16 months)
- Overall Survival (OS)(Up to approximately 16 months)