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

Neoplasm, Breast Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03368196
• Other study ID #: DS8201-A-A103
• Status: Completed
• Phase: Phase 1
• Start date: April 2, 2018
• Est. completion date: September 28, 2022

Study information

• Verified date: November 2022
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 28, 2022
• Est. primary completion date: September 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma, Gastric
• Breast Neoplasms
• Neoplasm, Breast

Intervention

Drug:
• DS-8201a
An antibody drug conjugate

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company	AstraZeneca

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-emergent Adverse Events Following Treatment With DS-8201a (Trastuzumab Deruxtecan)	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.	Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose
Secondary	Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)	Maximum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.	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
Secondary	Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)	Maximum concentration (Cmax) of MAAA-1181a was assessed.	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
Secondary	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)	Area under the serum concentration-time curve during dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody was assessed.	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
Secondary	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)	Area under the serum concentration-time curve during dosing interval (AUCtau) of MAAA-1181a was assessed.	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
Secondary	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	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.	Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose
Secondary	Objective Response Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer	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.	Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose
Secondary	Disease Control Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer	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.	Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose