Phase 1 Study of DS-6051b in Japanese Subjects With Advanced Solid Malignant Tumors

Study Overview
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Brief Summary
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This is a Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of DS-6051b in Japanese subjects with advanced solid malignant tumors harboring either a ROS1 or NTRK fusion gene.

Detailed Description
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This study is single arm study with DS-6051b in approximately 9 subjects with advanced solid malignant tumors harboring either a ROS1 or NTRK fusion gene. Safety and tolerability, pharmacokinetics (PK), maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) and preliminary efficacy of DS-6051b will be evaluated.

Official Title
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Phase 1 Study of DS-6051b in Japanese Subjects With Advanced Solid Malignant Tumors Harboring Either a ROS1 or NTRK Fusion Gene

Conditions
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Advanced Solid Malignant Tumors

Intervention / Treatment
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* Drug: DS-6051b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced solid malignant tumors that are refractory to standard therapy or for which no standard therapy is available. An Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. Exclusion Criteria: Previously had or currently has any of the following diseases: Cardiac failure (NYHA Functional Classification ≥ Class III), myocardial infarction, cerebral infarction, unstable angina, arrhythmia requiring treatment, coronary/peripheral artery disease, pulmonary thrombosis, uncontrolled deep vein thrombosis, clinically severe thromboembolic event, or autoimmune disease requiring treatment. Previously had or currently has clinically severe pulmonary disease (eg, interstitial pneumonia, pneumonitis, pulmonary fibrosis, radiation pneumonia). Severe or uncontrolled concomitant disease. Clinically active brain metastases or central nervous system tumor requiring steroid or anticonvulsant treatment.

Ages Eligible for Study
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Minimum Age: 20 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: DS-6051b<br>Drug: DS-6051b 400 mg or 800 mg daily | Drug: DS-6051b<br>* Drug: DS-6051b 400 mg or 800 mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number and severity of adverse events | number and severity of treatment emergent adverse events | Day 1 through 28 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of DS-6051a | Maximum concentration (Cmax), time to maximum plasma concentration (Tmax), area under the concentration-time curve (AUC) and CL/F for DS-6051a (a free base form of DS-6051b) will be assessed on Days 1 and 15 of Cycle 1. | Days 1 and 15 of Cycle 1 | 
| Tmax of DS-6051a | Maximum concentration (Cmax), time to maximum plasma concentration (Tmax), area under the concentration-time curve (AUC) and CL/F for DS-6051a (a free base form of DS-6051b) will be assessed on Days 1 and 15 of Cycle 1. | Days 1 and 15 of Cycle 1 | 
| AUC of DS-6051a | Maximum concentration (Cmax), time to maximum plasma concentration (Tmax), area under the concentration-time curve (AUC) and CL/F for DS-6051a (a free base form of DS-6051b) will be assessed on Days 1 and 15 of Cycle 1. | Days 1 and 15 of Cycle 1 | 
| clearance (CL/F) of DS-6051a | Maximum concentration (Cmax), time to maximum plasma concentration (Tmax), area under the concentration-time curve (AUC) and CL/F for DS-6051a (a free base form of DS-6051b) will be assessed on Days 1 and 15 of Cycle 1. | Days 1 and 15 of Cycle 1 | 
| Number of participants with dose-limiting toxicities | to determine maximum tolerated dose/recommended phase 2 dose | 21 days following the first dose of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumor, DS-6051b, ROS1, NTRK, refractory to standard therapy, no standard therapy