Phase 1, Open-label Study to Assess the Safety, Tolerability, and Pharmacokinetics of DS-8895a in Subjects With Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Daiichi Sankyo Co., Ltd.
- Enrollment
- 37
- Locations
- 2
- Primary Endpoint
- number of participants experiencing clinical or laboratory adverse events
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
dose escalation then expansion
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.
Intervention: DS-8895a (Drug)
Outcomes
Primary Outcomes
number of participants experiencing clinical or laboratory adverse events
Time Frame: from start of treatment to end of treatment, on expected average 12 weeks
to investigate the safety of DS-8895a reporting on frequency and seriousness of treatment emergent adverse events
serum pharmacokinetics of DS-8895a
Time Frame: 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
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
number of participants experiencing dose limiting toxicities
Time Frame: day 1 through day 28
to investigate the safety of DS-8895a reporting on frequency and seriousness of treatment emergent adverse events
Secondary Outcomes
- level of anti-DS-8895a (HAHA) antibody(Cycle 1 days 1 and 15; Cycle 2 day 1; end of study; 45 days post-last-dose)
- disease control rate(every 6 weeks)
- pharmacodynamic effects in tumors(baseline and day 1 of cycle 2)
- pharmacodynamic effects in blood(day 1 and 2)
- objective response rate(every 6 weeks)