Phase 1 Study of DS-8895a in Subjects With Advanced Solid Tumors
- Registration Number
- NCT02004717
- Lead Sponsor
- Daiichi Sankyo Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description dose escalation then expansion DS-8895a 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.
- Primary Outcome Measures
Name Time Method number of participants experiencing clinical or laboratory adverse events 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 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 day 1 through day 28 to investigate the safety of DS-8895a reporting on frequency and seriousness of treatment emergent adverse events
- Secondary Outcome Measures
Name Time Method 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 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"
disease control rate every 6 weeks proportion of subjects with the best overall response of stable disease or better will be measured every 6 weeks until study drug discontinued.
pharmacodynamic effects in tumors baseline and day 1 of cycle 2 effects on tumor cells will be determined at baseline and day 1 of cycle 2
pharmacodynamic effects in blood day 1 and 2 effects on blood will be determined at day 1 and 2 of each cycle
objective response rate every 6 weeks sum of complete response and partial response rates measured every 6 weeks until study drug discontinuation
Trial Locations
- Locations (2)
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Osaka University Hospital
🇯🇵Suita, Osaka, Japan