Phase 1 Study of DS-8895a in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, sequential dose escalation and expansion study to evaluate the safety, tolerability, and pharmacokinetics of DS-8895a in Japanese subjects with advanced solid tumors.

Official Title
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Phase 1, Open-label Study to Assess the Safety, Tolerability, and Pharmacokinetics of DS-8895a in Subjects With Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: DS-8895a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced solid tumor that is refractory to standard treatment, or for which no standard treatment is available. Eastern Cooperative Oncology Group performance status(PS) of 0 or 1 Exclusion Criteria: Have any of the following concomitant disease or had the history of having following disease within 6 months before enrollment: Cardiac failure (NYHA ≥ ClassIII), myocardial infarction, cerebral infarction, unstable angina, arrhythmia requiring treatment, coronary-artery/peripheral artery bypass surgery, cerebrovascular disease, pulmonary thromboembolism, deep-vein thrombosis or clinically severe thromboembolic event, or clinically severe pulmonary disease (eg, interstitial pneumonia, pulmonary fibrosis, radiation pneumonia, drug induced pneumonia) Severe or uncontrolled concomitant disease. Clinically active brain metastases defined as symptomatic or requiring 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: dose escalation then expansion<br>Dose escalation of this study will follow a 3+3 study design with a starting intravenous (IV) dose of 0.1 mg/kg. Six dose levels are planned: level 1,0.1 mg/kg; level 2,0.3 mg/kg; level 3, 1.0 mg/kg; level 4,3.0 mg/kg; level 5,10 mg/kg; level 6,20 mg/kg. Dose Expansion - Up to 20 subjects will be enrolled and treated at the dose determined in Dose Escalation arm. | Drug: DS-8895a<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of participants experiencing dose limiting toxicities | to investigate the safety of DS-8895a reporting on frequency and seriousness of treatment emergent adverse events | day 1 through day 28 | 
| number of participants experiencing clinical or laboratory adverse events | to investigate the safety of DS-8895a reporting on frequency and seriousness of treatment emergent adverse events | from start of treatment to end of treatment, on expected average 12 weeks | 
| serum pharmacokinetics of DS-8895a | pharmacokinetics (Area Under the Curve-AUC, Terminal Elimination half-life-t1/2, Total Body Clearance) of DS-8895a in Japanese subjects with advanced solid tumors, and also to investigate the recommended dose of DS-8895a for subsequent clinical studies | Cycle 1 - days 1, 2, 4, 8 and 15; Cycle 2-days 1, 2, 4, 8 and 15; Cycle 3 and on- days 1; end of study; 45 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| level of anti-DS-8895a (HAHA) antibody | Human anti-human antibody (HAHA) profile for DS-8895a [Time Frame: Cycle 1 - days 1, and 15; Cycle 2 and on - days 1; end of study; 45 days post last dose] The presence of HAHA (anti-DS-8895a neutralizing antibody) in serum will be assessed | Cycle 1 days 1 and 15; Cycle 2 day 1; end of study; 45 days post-last-dose | 
| disease control rate | proportion of subjects with the best overall response of stable disease or better will be measured every 6 weeks until study drug discontinued. | every 6 weeks | 
| pharmacodynamic effects in blood | effects on blood will be determined at day 1 and 2 of each cycle | day 1 and 2 | 
| pharmacodynamic effects in tumors | effects on tumor cells will be determined at baseline and day 1 of cycle 2 | baseline and day 1 of cycle 2 | 
| objective response rate | sum of complete response and partial response rates measured every 6 weeks until study drug discontinuation | every 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced solid tumor, Phase 1, Oncology