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

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

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 Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: DS-8895a

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: DS-8895a

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.

Publications and helpful links

General Publications

• Shitara K, Satoh T, Iwasa S, Yamaguchi K, Muro K, Komatsu Y, Nishina T, Esaki T, Hasegawa J, Kakurai Y, Kamiyama E, Nakata T, Nakamura K, Sakaki H, Hyodo I. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the afucosylated, humanized anti-EPHA2 antibody DS-8895a: a first-in-human phase I dose escalation and dose expansion study in patients with advanced solid tumors. J Immunother Cancer. 2019 Aug 14;7(1):219. doi: 10.1186/s40425-019-0679-9.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: November 15, 2013
• First Submitted That Met QC Criteria: December 3, 2013
• First Posted (Estimate): December 9, 2013

Study Record Updates

• Last Update Posted (Actual): July 22, 2019
• Last Update Submitted That Met QC Criteria: July 18, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Phase 1; Oncology; advanced solid tumor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: DS8895-A-J101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No