Clinical Trials List
Protocol NumberDS8201-A-U302
NCT Number(ClinicalTrials.gov Identfier)NCT03529110
2019-01-24 - 2020-12-31
Phase III
Recruiting5
ICD-10C50
Malignant neoplasm of breast
ICD-9174.9
Malignant neoplasm of female breast, unspecified
A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of DS-8201a (Trastuzumab Deruxtecan), an Anti-HER2 Antibody Drug Conjugate (ADC), Versus Ado Trastuzumab Emtansine (T-DM1) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With Trastuzumab and Taxane
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Daiichi Sankyo Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chen-Teng Wu Division of General Surgery
- Chih-Jung Chen Division of General Surgery
- HWEI-CHUNG WANG Division of General Surgery
- Yao-Chung Wu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wu-Chou Su Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Yao-Lung Kuo Division of General Surgery
- Kuo-Ting Lee Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- 褚乃銘 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ta-Chung Chao Division of Hematology & Oncology
- 邱仁輝 Division of General Surgery
- Chun-Yu Liu Division of Hematology & Oncology
- 林燕淑 Division of General Surgery
- Yi-Fang Tsai Division of General Surgery
- 林永慧 Division of Radiology
The Actual Total Number of Participants Enrolled
4 Recruiting
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 蔡立威 Division of General Surgery
- 張端瑩 Division of Hematology & Oncology
- MING-YANG WANG Division of General Surgery
- YEN-SHEN LU Division of Hematology & Oncology
- 張允中 Division of Radiology
- 郭文宏 Division of General Surgery
- Wei-Wu Chen Division of Hematology & Oncology
- 羅喬 Division of General Surgery
- 林季宏 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Breast Cancer
Objectives
Primary Objective
The primary objective is to compare the efficacy of DS-8201a to T-DM1 on PFS.
Secondary Objectives
The secondary objectives are:
To further compare the efficacy of DS-8201a compared to T-DM1 on:
OS;
ORR;
DoR;
Clinical benefit rate (CBR).
To further determine PK of DS-8201a;
To further evaluate safety of DS-8201a compared to T-DM1;
To evaluate Health Economic and Outcomes Research (HEOR) endpoints for
DS-8201a compared to T-DM1.
Exploratory Objectives
The exploratory objectives are:
To evaluate potential biomarkers (eg, serum HER2-extracellular domain
[HER2ECD]).
To evaluate exposure-response relationships for efficacy and safety endpoints.
Test Drug
DS-8201a
Active Ingredient
DS-8201a
Dosage Form
Lyophilized powder for injection
Dosage
100 mg
Endpoints
Primary Efficacy Endpoint
The primary efficacy endpoint is PFS as determined by blinded independent central
review (BICR).
Secondary Efficacy Endpoints
The secondary efficacy endpoints are:
OS
ORR based on BICR and investigator assessment
DoR based on BICR and investigator assessment
CBR based on BICR and investigator assessment
PFS based on investigator assessment
Exploratory Efficacy Endpoints
The exploratory efficacy endpoints are:
Duration of stable disease (SD) based on BICR and investigator assessment
Time to response based on BICR and investigator assessment
Best percent change in the sum of the diameter of measurable tumors based on
BICR and investigator assessment
Time to hospitalization, defined as the time from the date of randomization to
the date of the first hospitalization during the study
Health Economic and Outcomes Research Endpoints
The HEOR endpoints include:
European Organization for Research and Treatment of Cancer (EORTC)
quality of life questionnaire (QLQ)-C30
EORTC QLQ-BR45
EuroQol-5 dimensions-5 levels of severity (EQ-5D-5L)
Hospitalization-related endpoints
Pharmacokinetic Endpoints
The PK endpoints include:
Serum concentrations of DS-8201a, total anti-HER2 antibody, and
MAAA-1181a
Biomarker Endpoints
The biomarker endpoints include:
Serum biomarkers (eg, HER2ECD)
Other potential biomarkers (eg, cell free deoxyribonucleic acid [cfDNA],
RNA profiling)
Safety Endpoints
The safety endpoints include:
Serious adverse events (SAEs)
TEAEs
AESI
Discontinuations due to adverse events (DAEs)
Physical examination findings (including Eastern Cooperative Oncology
Group Performance Status [ECOG PS])
Vital sign measurements
Standard clinical laboratory parameters
Electrocardiogram (ECG) parameters
Echocardiogram (Echo)/multigated acquisition scan (MUGA) findings
Anti-drug antibodies (ADA)
The primary efficacy endpoint is PFS as determined by blinded independent central
review (BICR).
Secondary Efficacy Endpoints
The secondary efficacy endpoints are:
OS
ORR based on BICR and investigator assessment
DoR based on BICR and investigator assessment
CBR based on BICR and investigator assessment
PFS based on investigator assessment
Exploratory Efficacy Endpoints
The exploratory efficacy endpoints are:
Duration of stable disease (SD) based on BICR and investigator assessment
Time to response based on BICR and investigator assessment
Best percent change in the sum of the diameter of measurable tumors based on
BICR and investigator assessment
Time to hospitalization, defined as the time from the date of randomization to
the date of the first hospitalization during the study
Health Economic and Outcomes Research Endpoints
The HEOR endpoints include:
European Organization for Research and Treatment of Cancer (EORTC)
quality of life questionnaire (QLQ)-C30
EORTC QLQ-BR45
EuroQol-5 dimensions-5 levels of severity (EQ-5D-5L)
Hospitalization-related endpoints
Pharmacokinetic Endpoints
The PK endpoints include:
Serum concentrations of DS-8201a, total anti-HER2 antibody, and
MAAA-1181a
Biomarker Endpoints
The biomarker endpoints include:
Serum biomarkers (eg, HER2ECD)
Other potential biomarkers (eg, cell free deoxyribonucleic acid [cfDNA],
RNA profiling)
Safety Endpoints
The safety endpoints include:
Serious adverse events (SAEs)
TEAEs
AESI
Discontinuations due to adverse events (DAEs)
Physical examination findings (including Eastern Cooperative Oncology
Group Performance Status [ECOG PS])
Vital sign measurements
Standard clinical laboratory parameters
Electrocardiogram (ECG) parameters
Echocardiogram (Echo)/multigated acquisition scan (MUGA) findings
Anti-drug antibodies (ADA)
Inclution Criteria
1. Must be competent and able to comprehend, sign, and date an Institutional
Review Board (IRB) or Ethics Committee (EC) approved ICF before performance
of any study-specific procedures or tests.
2. Adults ≥18 y old. (Please follow local regulatory requirements if the legal age of
consent for study participation is >18 y old.)
3. Pathologically documented breast cancer that:
a. is unresectable or metastatic.
b. has confirmed HER2-positive expression as determined according to
American Society of Clinical Oncology – College of American Pathologists
guidelines evaluated at a central laboratory.
22
c. was previously treated with trastuzumab and taxane in the advanced/
metastatic setting or progressed within 6 mo after neoadjuvant or adjuvant
treatment involving a regimen including trastuzumab and taxane.
4. Documented radiologic progression (during or after most recent treatment or
within 6 mo after completing adjuvant therapy).
5. Subjects must be HER2-positive as confirmed by central laboratory assessment of
most recent tumor tissue sample available. If archived tissue is not available, a
fresh biopsy is required.
6. Presence of at least 1 measurable lesion per modified Response Evaluation
Criteria in Solid Tumors (mRECIST) version 1.1 (see Section 17.4).
23
7. ECOG PS 0 or 1.
8. Adequate bone marrow function, within 14 d before randomization, defined as:
Absolute neutrophil count ≥ 1.5 × 109
/L (granulocyte colony-stimulating
factor administration is not allowed within 1 wk prior to Screening
assessment);
Platelet count ≥ 100 × 109
/L (Platelet transfusion is not allowed within 1 wk
prior to Screening assessment);
Hemoglobin level ≥ 9.0 g/dL (Red blood cell transfusion is not allowed within
1 wk prior to Screening assessment).
9. Adequate renal function within 14 d before randomization, defined as:
Creatinine clearance ≥ 30 mL/min, as calculated using the Cockcroft-Gault
equation ([{140 – age in y} × {actual weight in kg}] divided by [{72 × serum
creatinine in mg/dL} multiply by 0.85 if female]; Section 17.2).
10. Adequate hepatic function within 14 d before randomization, defined as:
Total bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or
< 3 × ULN in the presence of documented Gilbert’s syndrome(unconjugated
hyperbilirubinemia) or liver metastases at baseline, and
Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 5 × ULN
11. Adequate blood clotting function within 14 d before randomization, defined as:
International normalized ratio/prothrombin time and activated partial
thromboplastin time ≤ 1.5 × ULN
12. Male and female subjects of reproductive/childbearing potential must agree to use
a highly effective form of contraception or avoid intercourse during and upon
completion of the study and for at least 4.5 mo after the last dose of DS-8201a or
7 mo after the last dose of T-DM1. Methods considered as highly effective
methods of contraception include:
Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation:
Oral
Intravaginal
Transdermal
Progestogen-only hormonal contraception associated with inhibition of
ovulation:
Oral
Injectable
Implantable
Intrauterine device
Intrauterine hormone-releasing system
Bilateral tubal occlusion
Vasectomized partner
Complete sexual abstinence defined as refraining from heterosexual
intercourse during and upon completion of the study and for at least 4.5 mo
after the last dose of DS-8201a or 7 mo after the last dose ofT-DM1. True
abstinence must be in line with the preferred and usual lifestyle of the subject.
Periodic abstinence (calendar, symptothermal, postovulation methods) is not
an acceptable method of contraception.
13. Male subjects must not freeze or donate sperm starting at Screening and
throughout the study period, and at least 4.5 mo after the last dose of DS-8201a or
7 mo after the last dose of T-DM1. Preservation of sperm should be considered
prior to enrollment in this study.
14. Female subjects must not donate ova or retrieve them for their own use from the
time of Screening and throughout the study treatment period, and for at least 4.5
mo after the last dose of DS-8201a or 7 mo after the last dose of T-DM1.
Review Board (IRB) or Ethics Committee (EC) approved ICF before performance
of any study-specific procedures or tests.
2. Adults ≥18 y old. (Please follow local regulatory requirements if the legal age of
consent for study participation is >18 y old.)
3. Pathologically documented breast cancer that:
a. is unresectable or metastatic.
b. has confirmed HER2-positive expression as determined according to
American Society of Clinical Oncology – College of American Pathologists
guidelines evaluated at a central laboratory.
22
c. was previously treated with trastuzumab and taxane in the advanced/
metastatic setting or progressed within 6 mo after neoadjuvant or adjuvant
treatment involving a regimen including trastuzumab and taxane.
4. Documented radiologic progression (during or after most recent treatment or
within 6 mo after completing adjuvant therapy).
5. Subjects must be HER2-positive as confirmed by central laboratory assessment of
most recent tumor tissue sample available. If archived tissue is not available, a
fresh biopsy is required.
6. Presence of at least 1 measurable lesion per modified Response Evaluation
Criteria in Solid Tumors (mRECIST) version 1.1 (see Section 17.4).
23
7. ECOG PS 0 or 1.
8. Adequate bone marrow function, within 14 d before randomization, defined as:
Absolute neutrophil count ≥ 1.5 × 109
/L (granulocyte colony-stimulating
factor administration is not allowed within 1 wk prior to Screening
assessment);
Platelet count ≥ 100 × 109
/L (Platelet transfusion is not allowed within 1 wk
prior to Screening assessment);
Hemoglobin level ≥ 9.0 g/dL (Red blood cell transfusion is not allowed within
1 wk prior to Screening assessment).
9. Adequate renal function within 14 d before randomization, defined as:
Creatinine clearance ≥ 30 mL/min, as calculated using the Cockcroft-Gault
equation ([{140 – age in y} × {actual weight in kg}] divided by [{72 × serum
creatinine in mg/dL} multiply by 0.85 if female]; Section 17.2).
10. Adequate hepatic function within 14 d before randomization, defined as:
Total bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or
< 3 × ULN in the presence of documented Gilbert’s syndrome(unconjugated
hyperbilirubinemia) or liver metastases at baseline, and
Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 5 × ULN
11. Adequate blood clotting function within 14 d before randomization, defined as:
International normalized ratio/prothrombin time and activated partial
thromboplastin time ≤ 1.5 × ULN
12. Male and female subjects of reproductive/childbearing potential must agree to use
a highly effective form of contraception or avoid intercourse during and upon
completion of the study and for at least 4.5 mo after the last dose of DS-8201a or
7 mo after the last dose of T-DM1. Methods considered as highly effective
methods of contraception include:
Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation:
Oral
Intravaginal
Transdermal
Progestogen-only hormonal contraception associated with inhibition of
ovulation:
Oral
Injectable
Implantable
Intrauterine device
Intrauterine hormone-releasing system
Bilateral tubal occlusion
Vasectomized partner
Complete sexual abstinence defined as refraining from heterosexual
intercourse during and upon completion of the study and for at least 4.5 mo
after the last dose of DS-8201a or 7 mo after the last dose ofT-DM1. True
abstinence must be in line with the preferred and usual lifestyle of the subject.
Periodic abstinence (calendar, symptothermal, postovulation methods) is not
an acceptable method of contraception.
13. Male subjects must not freeze or donate sperm starting at Screening and
throughout the study period, and at least 4.5 mo after the last dose of DS-8201a or
7 mo after the last dose of T-DM1. Preservation of sperm should be considered
prior to enrollment in this study.
14. Female subjects must not donate ova or retrieve them for their own use from the
time of Screening and throughout the study treatment period, and for at least 4.5
mo after the last dose of DS-8201a or 7 mo after the last dose of T-DM1.
Exclusion Criteria
1. Prior treatment with an anti-HER2 ADC.
2. Uncontrolled or significant cardiovascular disease, including any of the following:
a. History of myocardial infarction within 6 mo before randomization;
b. History of symptomatic congestive heart failure (New York Heart Association
Class II to IV);
c. Troponin levels consistent with myocardial infarction as defined according to
the manufacturer within 28 d prior to randomization;
d. Corrected QT interval (QTc) prolongation to > 470 ms (females) or >450 ms
(male) based on average of Screening triplicate 12-lead ECG;
e. Left ventricular ejection fraction (LVEF) < 50% within 28 d prior to
randomization
3. Has a history of (noninfectious) ILD/pneumonitis that required steroids, has
current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled
out by imaging at Screening.
4. Spinal cord compression or clinically active central nervous system (CNS)
metastases, defined as untreated and symptomatic, or requiring therapy with
corticosteroids or anticonvulsants to control associated symptoms.
Subjects with clinically inactive brain metastases may be included in the
study.
Subjects with treated brain metastases that are no longer symptomatic and
who require no treatment with corticosteroids or anticonvulsants may be
included in the study if they have recovered from the acute toxic effect of
radiotherapy. A minimum of 2 wk must have elapsed between the end of
whole brain radiotherapy and study enrollment.
5. Has a history of severe hypersensitivity reactions to either the drug substances or
inactive ingredients in the drug product.
6. History of severe hypersensitivity reactions to other mAbs.
7. Substance abuse or medical conditions such as clinically significant cardiac or
pulmonary diseases or psychological conditions, that would, in the opinion of the
investigator, increase the safety risk to the subject or interfere with the subject’s
participation in the clinical study or evaluation of the clinical study results.
8. Social, familial, or geographical factors that would interfere with study
participation or follow-up.
9. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
10. Known human immunodeficiency virus (HIV) infection or active hepatitis B or C
infection. Subjects should be tested for HIV prior to randomization if required by
local regulations or IRB/EC.
11. Multiple primary malignancies within 3 y, except adequately resected nonmelanoma skin cancer, curatively treated in situ disease, or contralateral breast
cancer.
12. Unresolved toxicities from previous anticancer therapy, defined as toxicities
(other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Subjects with
chronic Grade 2 toxicities may be eligible per the discretion of the investigator
after consultation with the Sponsor Medical Monitor or designee (eg, Grade 2
chemotherapy-induced neuropathy).
13. Therapeutic radiation therapy or major surgery within 4 wk before study
treatment or palliative stereotactic radiation therapy (other than abdominal
radiation) within 2 wk before study treatment.
14. Systemic treatment with anticancer therapy, antibody-based therapy, retinoid
therapy, or hormonal therapy within 3 wk before study treatment; or treatment
with nitrosoureas or mitomycin C within 6 wk before study treatment; or
treatment with small-molecule targeted agents within 2 wk or 5 half-lives before
study treatment, whichever is longer.
15. Current treatment with strong cytochrome P450 (CYP3A4) and organic anion
transporting polypeptide (OATP) inhibitors (see Section 17.6) and any mAb
treatment (washout period of ≥ 3 elimination half-lives of the inhibitor/antibody is
required).
16. Participation in a therapeutic clinical study within 3 wk before study treatment
(for small-molecule targeted agents, this non-participation period is 2 wk or 5
half-lives, whichever is longer), or current participation in other investigational
procedures.
17. Pregnant, breastfeeding, or planning to become pregnant.
18. Subject must not be an immediate family member of study site personnel or of
Sponsor personnel.
19. Otherwise considered inappropriate for the study by the investigator.
2. Uncontrolled or significant cardiovascular disease, including any of the following:
a. History of myocardial infarction within 6 mo before randomization;
b. History of symptomatic congestive heart failure (New York Heart Association
Class II to IV);
c. Troponin levels consistent with myocardial infarction as defined according to
the manufacturer within 28 d prior to randomization;
d. Corrected QT interval (QTc) prolongation to > 470 ms (females) or >450 ms
(male) based on average of Screening triplicate 12-lead ECG;
e. Left ventricular ejection fraction (LVEF) < 50% within 28 d prior to
randomization
3. Has a history of (noninfectious) ILD/pneumonitis that required steroids, has
current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled
out by imaging at Screening.
4. Spinal cord compression or clinically active central nervous system (CNS)
metastases, defined as untreated and symptomatic, or requiring therapy with
corticosteroids or anticonvulsants to control associated symptoms.
Subjects with clinically inactive brain metastases may be included in the
study.
Subjects with treated brain metastases that are no longer symptomatic and
who require no treatment with corticosteroids or anticonvulsants may be
included in the study if they have recovered from the acute toxic effect of
radiotherapy. A minimum of 2 wk must have elapsed between the end of
whole brain radiotherapy and study enrollment.
5. Has a history of severe hypersensitivity reactions to either the drug substances or
inactive ingredients in the drug product.
6. History of severe hypersensitivity reactions to other mAbs.
7. Substance abuse or medical conditions such as clinically significant cardiac or
pulmonary diseases or psychological conditions, that would, in the opinion of the
investigator, increase the safety risk to the subject or interfere with the subject’s
participation in the clinical study or evaluation of the clinical study results.
8. Social, familial, or geographical factors that would interfere with study
participation or follow-up.
9. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
10. Known human immunodeficiency virus (HIV) infection or active hepatitis B or C
infection. Subjects should be tested for HIV prior to randomization if required by
local regulations or IRB/EC.
11. Multiple primary malignancies within 3 y, except adequately resected nonmelanoma skin cancer, curatively treated in situ disease, or contralateral breast
cancer.
12. Unresolved toxicities from previous anticancer therapy, defined as toxicities
(other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Subjects with
chronic Grade 2 toxicities may be eligible per the discretion of the investigator
after consultation with the Sponsor Medical Monitor or designee (eg, Grade 2
chemotherapy-induced neuropathy).
13. Therapeutic radiation therapy or major surgery within 4 wk before study
treatment or palliative stereotactic radiation therapy (other than abdominal
radiation) within 2 wk before study treatment.
14. Systemic treatment with anticancer therapy, antibody-based therapy, retinoid
therapy, or hormonal therapy within 3 wk before study treatment; or treatment
with nitrosoureas or mitomycin C within 6 wk before study treatment; or
treatment with small-molecule targeted agents within 2 wk or 5 half-lives before
study treatment, whichever is longer.
15. Current treatment with strong cytochrome P450 (CYP3A4) and organic anion
transporting polypeptide (OATP) inhibitors (see Section 17.6) and any mAb
treatment (washout period of ≥ 3 elimination half-lives of the inhibitor/antibody is
required).
16. Participation in a therapeutic clinical study within 3 wk before study treatment
(for small-molecule targeted agents, this non-participation period is 2 wk or 5
half-lives, whichever is longer), or current participation in other investigational
procedures.
17. Pregnant, breastfeeding, or planning to become pregnant.
18. Subject must not be an immediate family member of study site personnel or of
Sponsor personnel.
19. Otherwise considered inappropriate for the study by the investigator.
The Estimated Number of Participants
-
Taiwan
71 participants
-
Global
500 participants
