DS-8201a in Patients With Cancer That Tests Positive for Human Epidermal Growth Factor Receptor 2 (HER2) Protein

• ClinicalTrials.gov Identifier: NCT03368196
• Recruitment Status: Completed
• First Posted: December 11, 2017
• Results First Posted: June 14, 2021
• Last Update Posted: November 3, 2022
• Sponsor: Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Daiichi Sankyo, Inc. ( Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company )

Study Description

Brief Summary:

HER2-positive cancer is a cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). HER2 promotes the growth of certain cancer cells. This study will test DS-8201a (trastuzumab deruxtecan), a HER2-targeted antibody and topoisomerase I inhibitor conjugate.

The safety and tolerability profile of DS-8201a will be assessed in Chinese patients with certain types of stomach and breast cancer that test positive for HER2. It also will test how DS-8201a moves within the body (pharmacokinetics).

Condition or disease	Intervention/treatment	Phase
Adenocarcinoma, Gastric; Neoplasm, Breast	Drug: DS-8201a	Phase 1

Detailed Description:

The expected time from the first subject's enrollment until the last subject's enrollment is approximately 8 months. The screening period is 28 days and each cycle of treatment is 21 days.

The number of treatment cycles is not fixed in this study. Subjects who continue to derive clinical benefit from the study drug in the absence of withdrawal of consent, progressive disease (PD), or unacceptable toxicity may continue the study drug.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1, Multicenter, Open-label Study of DS-8201a to Assess Safety and Pharmacokinetics in Subjects With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
• Actual Study Start Date: April 2, 2018
• Actual Primary Completion Date: September 14, 2018
• Actual Study Completion Date: September 28, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: DS-8201a; DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks (Q3W)	Drug: DS-8201a; An antibody drug conjugate

Outcome Measures

Primary Outcome Measures :

1. Treatment-emergent Adverse Events Following Treatment With DS-8201a (Trastuzumab Deruxtecan) [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose ]
   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.

Secondary Outcome Measures :

1. Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan) [ Time Frame: Cycles 1 and 3, Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4, 24 hours, 72 hours; Days 8, and 15; Cycles 2, 4, 6 and 8, Day 1: BI and EOI ]
   Maximum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
2. Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan) [ Time Frame: Cycles 1 and 3, Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4, 24 hours, 72 hours; Days 8, and 15; Cycles 2, 4, 6 and 8, Day 1: BI and EOI ]
   Maximum concentration (Cmax) of MAAA-1181a was assessed.
3. Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan) [ Time Frame: Cycles 1 and 3, Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4, 24 hours, 72 hours; Days 8, and 15; Cycles 2, 4, 6 and 8, Day 1: BI and EOI ]
   Area under the serum concentration-time curve during dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody was assessed.
4. Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan) [ Time Frame: Cycles 1 and 3, Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4, 24 hours, 72 hours; Days 8, and 15; Cycles 2, 4, 6 and 8, Day 1: BI and EOI ]
   Area under the serum concentration-time curve during dosing interval (AUCtau) of MAAA-1181a was assessed.
5. Best Overall Response By The Investigator's Assessment (Unconfirmed) in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose ]
   Best overall response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Complete response (CR) was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
6. Objective Response Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose ]
   Objective response rate (ORR; defined as participants who achieved CR and PR) was 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.
7. Disease Control Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose ]
   Disease control rate (DCR; defined as participants who achieved CR, PR, and SD) was 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, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Has a pathologically documented unresectable or metastatic gastric or GEJ adenocarcinoma, or breast cancer, with HER2 expression [immunohistochemistry (IHC) 3+, 2+, or 1+ and/or in situ hybridization (ISH) +] that is refractory to or intolerable with standard treatment, or for which no standard treatment is available
• Has a left ventricular ejection fraction (LVEF) ≥ 50%
• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1

Exclusion Criteria:

• Has a medical history of myocardial infarction within 6 months before enrollment
• Has a medical history of ventricular arrhythmias, other than rare occasional premature ventricular contractions
• Has uncontrolled or significant cardiovascular disease

• Has any other history or condition that might compromise:

  1. Safety of the participant or offspring
  2. Safety of study staff
  3. Analysis of Results

Contacts and Locations

Locations

Taiwan

National Taiwan University Hospital

Taipei, Taiwan, 100

Taipei Veterans General Hospital

Taipei, Taiwan, 112

Sponsors and Collaborators

Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company

AstraZeneca

Investigators

• Study Director: Global Clinical Leader; Daiichi Sankyo, Inc.

  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company ):

Study Protocol and Statistical Analysis Plan  [PDF] July 3, 2020

More Information

• Responsible Party: Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company
• ClinicalTrials.gov Identifier: NCT03368196
• Other Study ID Numbers: DS8201-A-A103
• First Posted: December 11, 2017
• Results First Posted: June 14, 2021
• Last Update Posted: November 3, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: 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/
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company ):

Stomach cancer; Cancer where the esophagus meets the stomach; Human epidermal growth factor 2; HER2; Breast Cancer; Adenocarcinoma, Gastroesophageal Junction (GEJ); Gastric Cancer; Antibody drug conjugate (ADC); Oncology

Additional relevant MeSH terms:

Adenocarcinoma; Breast Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Trastuzumab deruxtecan; Immunoconjugates; Immunologic Factors; Physiological Effects of Drugs