Safety and Pharmacokinetics of Tucatinib (MK-7119) in Chinese Participants With Cancer (MK-7119-002)

Study Overview
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Brief Summary
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The primary purpose of this study is to characterize the safety and tolerability of tucatinib (MK-7119) in Chinese participants with human epidermal growth factor receptor 2 positive (HER2+) advanced breast cancer, gastric or gastroesophageal junction adenocarcinoma (GEC), and colorectal cancer.

Official Title
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A Phase 1 Clinical Study to Investigate the Safety and Pharmacokinetics of Tucatinib (MK-7119) in China Participants With HER2+ Advanced Breast Cancer, Gastric or Gastroesophageal Junction Adenocarcinoma and Colorectal Cancer

Conditions
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Metastatic HER2+ Advanced Breast Cancer, Breast Neoplasms, Gastric or Gastroesophageal Junction Adenocarcinoma (GEC), Colorectal Cancer

Intervention / Treatment
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* Drug: Tucatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed HER2+ advanced breast cancer, gastric or GEC, and colorectal cancer Have progressed at least one previous therapeutic regimen and either no longer are candidates for standard therapy, have no standard therapy available, or choose not to pursue standard therapy Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance within 7 days prior to allocation Has life expectancy >6 months in the opinion of the investigator Have measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by the local site investigator/radiologist Must test negative for hepatitis B surface antigen (HBsAg) If there is a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load at screening For males, agree to be abstinent from heterosexual intercourse, or agree to use acceptable contraception, for the duration of study and 1 week after For females, is not pregnant or breastfeeding AND one of the following applies: Is not a woman of childbearing potential (WOCBP) Is a WOCBP and uses highly effective contraception and is not pregnant Exclusion Criteria: History of prior cancer within <3 year, except for adequately treated basal cell or squamous cell carcinoma of the skin, cervical cancer in situ, or other in situ carcinomas which needs discussion between the investigator and the Sponsor Participants with leptomeningeal disease are excluded Has symptomatic central nervous system (CNS) metastases Has active human immunodeficiency virus (HIV), hepatitis B virus, or HCV infection Has had chemotherapy, immunotherapy, radioimmunotherapy, definitive radiation, or biological cancer therapy or treatment with an investigational product within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention Has an active infection requiring therapy Has refractory nausea/vomiting, chronic gastrointestinal disease, or significant bowel resection Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study Has a QTc prolongation Has uncontrolled illness including but not limited to ongoing symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness that would limit compliance with study requirements Has had major surgery within 4 weeks prior to first dose of study intervention Is currently participating in another clinical trial Has psychiatric or substance abuse disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tucatinib Treatment<br>Chinese participants with HER2+ advanced breast cancer, gastric or gastroesophageal junction adenocarcinoma, or colorectal cancer receive tucatinib 300 mg by mouth twice daily during 21-day cycles. Treatment continues until there is evidence of unacceptable toxicity or documented progression. | Drug: Tucatinib<br>* Tucatinib 150 mg and 50 mg tablets taken by mouth at a dose of 300 mg twice daily.<br>* Other names: MK-7119;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with ≥1 adverse event (AE) | 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. | Up to approximately 19 months | 
| Percentage of participants discontinuing from study therapy due to AE | 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. | Up to approximately 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of first dose of tucatinib | The Cmax of tucatinib will be determined after the first dose. | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Time of maximum plasma concentration (Tmax) of first dose of tucatinib | The Tmax of tucatinib will be determined after the first dose. | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Area under the plasma concentration time curve from dosing to 12 hours postdose (AUC0-12) of first dose of tucatinib | The AUC0-12 of tucatinib will be determined after the first dose. | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Apparent plasma half-life (t½) of first dose of tucatinib | The t½ of tucatinib will be determined after the first dose. | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Apparent clearance (CL/F) of first dose of tucatinib | The CL/F of tucatinib will be determined after the first dose. | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Volume of distribution (Vz/F) of first dose of tucatinib | The Vz/F of tucatinib will be determined after the first dose. | Cycle 1, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Trough concentration (Ctrough) of tucatinib at steady state | The Ctrough of tucatinib will be determined at steady state. | Cycle 1, Days 8 and 15: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Accumulation ratio of tucatinib at steady state | The accumulation ratio of tucatinib will be determined at steady state. | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Cmax at steady state (Cmaxss) of tucatinib | The Cmaxss of tucatinib will be determined at steady state. | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Tmax at steady state (Tmaxss) of tucatinib | The Tmaxss of tucatinib will be determined at steady state. | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| AUC0-12 at steady state (AUC0-12ss) of tucatinib | The AUC0-12ss of tucatinib will be determined at steady state. | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| t½ of tucatinib at steady state | The t½ of tucatinib will be determined at steady state. | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| CL/F at steady state (CL/Fss) of tucatinib | The CL/Fss of tucatinib will be determined at steady state. | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Vz/F at steady state (Vz/Fss) of tucatinib | The Vz/Fss of tucatinib will be determined at steady state. | Cycle 2, Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose | 
| Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | ORR is defined as the percentage of participants who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR based on RECIST 1.1 will be presented. | Up to approximately 19 months | 
| Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. | Up to approximately 19 months |