Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Immunoglobulins

Trastuzumab

Trastuzumab deruxtecan

Immunoconjugates

Immunologic Factors

All participants will receive DS-8201a by intravenous infusion

DS-8201a is supplied as a lyophilized powder which is reconstituted for infusion

DS-8201a

Global Clinical Leader

This study will look at the effect on the QTc interval and pharmacokinetics after multiple dosing in subjects with HER2-expressing metastatic and/or unresectable breast cancer.

Phase 1 Study to Evaluate the Effect of DS-8201a on the QT/QTc Interval and Pharmacokinetics in HER2-Expressing Breast Cancer

Phase 1, Multicenter, Open-label, Multiple-dose Study of DS-8201a to Assess the Effect on the QT Interval and Pharmacokinetics in Subjects With HER2-expressing Metastatic and/or Unresectable Breast Cancer

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

The number of participants with notable electrocardiogram changes meeting predefined criteria is being reported.

Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.

Maximum serum concentration (Cmax) of MAAA-1181 was assessed.

Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody were assessed.

Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) were assessed.

Objective response rate (ORR) was defined as unconfirmed complete response (CR) and partial response (PR) as assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

Adverse events (AEs) were to be coded using MedDRA Version 20.1 and assigned severity grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiating the study drug until 47 days after last dose of study drug.

AstraZeneca

Daiichi Sankyo Co., Ltd.

Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.

Age, Continuous

≥65

Age, Customized

Sex: Female, Male

Race (NIH/OMB)

Japan

Region of Enrollment

Contact for Clinical Trial Information

Maximum change from baseline in QTcF: >30 ms

Maximum change from baseline in QTcF: >60 ms

QTc and QTcF were assessed in the Cardiac Analysis Set.

Changes in QTcF After Treatment With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

DS-8201: Cycle 1

DS-8201: Cycle 3

Total Anti-HER2 antibody: Cycle 1

Total Anti-HER2 antibody: Cycle 3

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

MAAA-1181a: Cycle 1

MAAA-1181a: Cycle 3

Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of MAAA-1181 After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

AUClast, DS-8201: Cycle 1

AUClast, Total Anti-HER2 antibody: Cycle 1

AUCtau, DS-8201: Cycle 1

AUCtau, DS-8201: Cycle 3

AUCtau, Total Anti-HER2 antibody: Cycle 1

AUCtau, Total Anti-HER2 antibody: Cycle 3

Pharmacokinetic Parameters Area Under the Concentration-Time Curve After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

AUClast, MAAA-1181a: Cycle 1

AUCtau, MAAA-1181a: Cycle 1

AUCtau, MAAA-1181a: Cycle 3

Pharmacokinetic Parameters Area Under the Concentration-Time Curve of MAAA-1181 After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

Participants with HER2 positive expression (defined as immunohistochemistry 3+ or in situ hybridization positive) who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.

HER2 Positive

Participants with HER2 low expression (defined as immunohistochemistry 1+ or 2+/ in situ hybridization negative or missing) who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.

HER2 Low

Response was assessed in the Efficacy Analysis Set.

Objective Response Rate Based on The Investigator's Assessment (Unconfirmed) Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

Any TEAEs

Gastrointestinal Disorders

Nausea

Vomiting

Constipation

Stomatitis

Diarrhoea

Investigations

Neutrophil count decreased

White blood cell count decreased

Platelet count decreased

Lymphocyte count decreased

Alanine aminotransferase increased

Aspartate aminotransferase increased

Blood and Lymphatic System Disorders

Anaemia

Skin and Subcutaneous Tissue Disorders

Alopecia

General Disorders and Administration Site Conditions

Fatigue

Infections and Infestations

Nasopharyngitis

Metabolism and Nutrition Disorders

Decreased appetite

Nervous System Disorders

Respiratory, Thoracic, and Mediastinal Disorders

Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.

Treatment-Emergent Adverse Events of Any Grade by System Organ Classes and Preferred Term Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer

Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Overall Study

Spots Global Cancer Trial Database for Phase 1 Study to Evaluate the Effect of DS-8201a on the QT/QTc Interval and Pharmacokinetics in HER2-Expressing Breast Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial