Clinical Trials List
Protocol NumberSGNTUC-016
NCT Number(ClinicalTrials.gov Identfier)NCT03975647
Active
2022-01-01 - 2026-09-23
Phase III
Not yet recruiting4
ICD-10C50.011
Malignant neoplasm of nipple and areola, right female breast
ICD-10C50.012
Malignant neoplasm of nipple and areola, left female breast
ICD-10C50.019
Malignant neoplasm of nipple and areola, unspecified female breast
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9174.0
Malignant neoplasm of female breast, nipple and areola
Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Subjects With Unresectable Locally-advanced or Metastatic HER2+ Breast Cancer (HER2CLIMB-02)
-
Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
-
Sponsor
Seagen Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Wei-Pang Chung Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- MING-YANG WANG Division of General Surgery
- YEN-SHEN LU Division of General Surgery
- 陳怡君 Division of General Surgery
- 羅喬 Division of General Surgery
- 林季宏 Division of General Surgery
- 蔡立威 Division of General Surgery
- Wei-Wu Chen Division of General Surgery
- 林柏翰 Division of General Surgery
- 張端瑩 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 沈士哲 Division of General Surgery
- Wen-Chi Shen Division of General Surgery
- 周旭桓 Division of General Surgery
- Mengting Peng Division of General Surgery
- Chi-Chang Yu Division of General Surgery
- Yung-Chang Lin Division of General Surgery
- Wen-Ling Kuo Division of General Surgery
- Chan-Keng Yang Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
HER2-positive Breast Cancer
Objectives
Primary:
PFS per RECIST v1.1, as determined by investigator assessment
Secondary:
OS
ORR per RECIST v1.1, by investigator
assessment
Other Secondary:
PFS per RECIST v1.1, as determined by BICR
PFS per RECIST v1.1, by investigator assessment in subjects with brain metastases at baseline
PFS per RECIST v1.1, by BICR in subjects with brain metastases at baseline
ORR per RECIST v1.1, by BICR
DOR per RECIST v1.1, by investigator assessment
DOR per RECIST v1.1, by BICR
CBR per RECIST v1.1, by investigator assessment
CBR per RECIST v1.1, by BICR
Incidence of AEs
Exploratory:
PK parameters for tucatinib and DM1
HCRU based on the number of medical care encounters and other procedures of interest
QoL measured by the EQ-5D-3L, EORTC QLQC30, NCI-PRO-CTCAE, and FACT-B
Test Drug
Tucatinib TabletsTucatinib Tablets
Active Ingredient
Tucatinib
Tucatinib
Tucatinib
Tucatinib
Tucatinib
Tucatinib
Tucatinib
Dosage Form
Tablet
Tablet
Tablet
Dosage
50 mg
150 mg
50 mg
150 mg
150 mg
50 mg
150 mg
Endpoints
PFS per RECIST v1.1, as determined by investigator assessment
Inclution Criteria
. Histologically confirmed HER2+ breast carcinoma, as determined by sponsor-designated
central laboratory testing on tumor tissue submitted prior to randomization (see Section
7.1.1), from either:
a. Archival tissue (most recent tumor tissue sample preferred)
b. If archival tissue is not available, then a newly-obtained baseline biopsy of an
accessible tumor lesion that has not been previously irradiated is required
2. History of prior treatment with a taxane and trastuzumab in any setting, separately or in
combination. Prior pertuzumab therapy is allowed, but not required.
3. Have progression of unresectable LA/M breast cancer after last systemic therapy (as
confirmed by investigator), or be intolerant of last systemic therapy
4. Measurable or non-measurable disease assessable by RECIST v1.1
5. HR (estrogen receptor [ER]/ progesterone receptor [PR]) status must be known prior to
randomization
6. Age ≥18 years at time of consent or ≥ the age of majority in the geographic location
7. ECOG performance status score of 0 or 1 (see APPENDIX B for conversion of
performance status using Karnofsky scale, if applicable)
8. Life expectancy ≥6 months, in the opinion of the investigator
9. Adequate hepatic function as defined by the following:
a. Total bilirubin ≤ 1.5 X upper limit of normal (ULN), except for subjects with known
Gilbert’s disease, who may enroll if the conjugated bilirubin is ≤1.5 X ULN
b. Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase
[AST/SGOT] and alanine aminotransferase/serum glutamic pyruvic transaminase
[ALT/SGPT]) ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases are present)
10. Adequate baseline hematologic parameters as defined by:
a. Absolute neutrophil count ≥1.0 X 103 /µL
b. Platelet count ≥100 X 103 /µL
c. Hemoglobin ≥9 g/dL
d. In subjects transfused before study entry, transfusion must be ≥14 days prior to start of therapy to establish adequate hematologic parameters independent from transfusion support
11. Estimated glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) study equation (see Section 7.7.4).
12. International normalized ratio (INR) and partial thromboplastin time (PTT)/activated
partial thromboplastin time (aPTT) ≤ 1.5 X ULN, unless on medication known to alter INR and PTT/aPTT.
13. Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiogram (ECHO)
or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose
of study treatment (see Section 6.2.2 for exceptions)
14. For subjects of childbearing potential, as defined in Section 4.3, the following stipulations apply:
a. Must have a negative serum or urine pregnancy test (minimum sensitivity of
25 mIU/mL or equivalent units of beta human chorionic gonadotropin [β-hCG]) result
within 7 days prior to the first dose of study treatment. A subject with a false positive
result and documented verification that the subject is not pregnant is eligible for
participation.
b. Must agree not to try to become pregnant during the study and for at least 7 months
after the final dose of study drug administration
c. Must agree not to breastfeed or donate ova, starting at time of informed consent and
continuing through 7 months after the final dose of study drug administration
d. If sexually active in a way that could lead to pregnancy, must consistently use
2 highly effective methods of birth control (as defined in Appendix K) starting at the
time of informed consent and continuing throughout the study and for at least
7 months after the final dose of study drug administration.
15. For subjects who can father children, the following stipulations apply:
a. Must agree not to donate sperm starting at time of informed consent and continuing
throughout the study period and for at least 7 months after the final study drug
administration
b. If sexually active with a person of childbearing potential in a way that could lead to
pregnancy, must consistently use 2 highly effective methods of birth control (as
defined in Appendix K) starting at time of informed consent and continuing
throughout the study and for at least 7 months after the final dose of study drug
administration
c. If sexually active with a person who is pregnant or breastfeeding, must consistently
use 1 of 2 highly effective methos of birth control (as defined in Appendix K) starting
at time of informed consent and continuing throughout the study and for at least
7 months after the final dose of study drug administration
16. The subject must provide written informed consent
17. Subject must be willing and able to comply with study procedures
18. CNS Inclusion – Based on screening contrast brain magnetic resonance imaging (MRI),
subjects must have at least one of the following:
a. No evidence of brain metastases
b. Untreated brain metastases not needing immediate local therapy. For subjects with
untreated CNS lesions >2.0 cm in diameter on screening contrast brain MRI, approval
from the medical monitor is required prior to enrollment.
c. Previously treated brain metastases
i. Brain metastases previously treated with local therapy may either be stable since
treatment or may have progressed since prior local CNS therapy, provided that
there is no clinical indication for immediate re-treatment with local therapy in the
opinion of the investigator
ii. Subjects treated with CNS local therapy for newly identified lesions or previously
treated and progressing lesions found on contrast brain MRI performed during
screening for this study may be eligible to enroll if all of the following criteria are
met:
• Time since SRS is ≥7 days prior to first dose of study treatment, time since
whole-brain radiation therapy (WBRT) is ≥14 days prior to first dose of study
treatment, or time since surgical resection is ≥28 days
• Other sites of evaluable disease are present
iii. Relevant records of any CNS treatment must be available to allow for
classification of target and non-target lesions
central laboratory testing on tumor tissue submitted prior to randomization (see Section
7.1.1), from either:
a. Archival tissue (most recent tumor tissue sample preferred)
b. If archival tissue is not available, then a newly-obtained baseline biopsy of an
accessible tumor lesion that has not been previously irradiated is required
2. History of prior treatment with a taxane and trastuzumab in any setting, separately or in
combination. Prior pertuzumab therapy is allowed, but not required.
3. Have progression of unresectable LA/M breast cancer after last systemic therapy (as
confirmed by investigator), or be intolerant of last systemic therapy
4. Measurable or non-measurable disease assessable by RECIST v1.1
5. HR (estrogen receptor [ER]/ progesterone receptor [PR]) status must be known prior to
randomization
6. Age ≥18 years at time of consent or ≥ the age of majority in the geographic location
7. ECOG performance status score of 0 or 1 (see APPENDIX B for conversion of
performance status using Karnofsky scale, if applicable)
8. Life expectancy ≥6 months, in the opinion of the investigator
9. Adequate hepatic function as defined by the following:
a. Total bilirubin ≤ 1.5 X upper limit of normal (ULN), except for subjects with known
Gilbert’s disease, who may enroll if the conjugated bilirubin is ≤1.5 X ULN
b. Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase
[AST/SGOT] and alanine aminotransferase/serum glutamic pyruvic transaminase
[ALT/SGPT]) ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases are present)
10. Adequate baseline hematologic parameters as defined by:
a. Absolute neutrophil count ≥1.0 X 103 /µL
b. Platelet count ≥100 X 103 /µL
c. Hemoglobin ≥9 g/dL
d. In subjects transfused before study entry, transfusion must be ≥14 days prior to start of therapy to establish adequate hematologic parameters independent from transfusion support
11. Estimated glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) study equation (see Section 7.7.4).
12. International normalized ratio (INR) and partial thromboplastin time (PTT)/activated
partial thromboplastin time (aPTT) ≤ 1.5 X ULN, unless on medication known to alter INR and PTT/aPTT.
13. Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiogram (ECHO)
or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose
of study treatment (see Section 6.2.2 for exceptions)
14. For subjects of childbearing potential, as defined in Section 4.3, the following stipulations apply:
a. Must have a negative serum or urine pregnancy test (minimum sensitivity of
25 mIU/mL or equivalent units of beta human chorionic gonadotropin [β-hCG]) result
within 7 days prior to the first dose of study treatment. A subject with a false positive
result and documented verification that the subject is not pregnant is eligible for
participation.
b. Must agree not to try to become pregnant during the study and for at least 7 months
after the final dose of study drug administration
c. Must agree not to breastfeed or donate ova, starting at time of informed consent and
continuing through 7 months after the final dose of study drug administration
d. If sexually active in a way that could lead to pregnancy, must consistently use
2 highly effective methods of birth control (as defined in Appendix K) starting at the
time of informed consent and continuing throughout the study and for at least
7 months after the final dose of study drug administration.
15. For subjects who can father children, the following stipulations apply:
a. Must agree not to donate sperm starting at time of informed consent and continuing
throughout the study period and for at least 7 months after the final study drug
administration
b. If sexually active with a person of childbearing potential in a way that could lead to
pregnancy, must consistently use 2 highly effective methods of birth control (as
defined in Appendix K) starting at time of informed consent and continuing
throughout the study and for at least 7 months after the final dose of study drug
administration
c. If sexually active with a person who is pregnant or breastfeeding, must consistently
use 1 of 2 highly effective methos of birth control (as defined in Appendix K) starting
at time of informed consent and continuing throughout the study and for at least
7 months after the final dose of study drug administration
16. The subject must provide written informed consent
17. Subject must be willing and able to comply with study procedures
18. CNS Inclusion – Based on screening contrast brain magnetic resonance imaging (MRI),
subjects must have at least one of the following:
a. No evidence of brain metastases
b. Untreated brain metastases not needing immediate local therapy. For subjects with
untreated CNS lesions >2.0 cm in diameter on screening contrast brain MRI, approval
from the medical monitor is required prior to enrollment.
c. Previously treated brain metastases
i. Brain metastases previously treated with local therapy may either be stable since
treatment or may have progressed since prior local CNS therapy, provided that
there is no clinical indication for immediate re-treatment with local therapy in the
opinion of the investigator
ii. Subjects treated with CNS local therapy for newly identified lesions or previously
treated and progressing lesions found on contrast brain MRI performed during
screening for this study may be eligible to enroll if all of the following criteria are
met:
• Time since SRS is ≥7 days prior to first dose of study treatment, time since
whole-brain radiation therapy (WBRT) is ≥14 days prior to first dose of study
treatment, or time since surgical resection is ≥28 days
• Other sites of evaluable disease are present
iii. Relevant records of any CNS treatment must be available to allow for
classification of target and non-target lesions
Exclusion Criteria
Prior treatment with tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other
investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with
lapatinib or neratinib within 12 months of starting study treatment (except in cases where
they were given for ≤21 days and was discontinued for reasons other than disease
progression or severe toxicity). Prior treatment with pyrotinib for recurrent or mBC
(except in cases where pyrotinib was given for ≤21 days and was discontinued for
reasons other than disease progression or severe toxicity)
Prior treatment with T-DM1 in any treatment setting
3. History of allergic reactions to trastuzumab or compounds chemically or biologically
similar to tucatinib, except for Grade 1 or 2 infusion-related reactions to trastuzumab that
were successfully managed, or known allergy to any of the excipients in the study drugs
4. Treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS
radiation, experimental agent or participation in another interventional clinical trial
≤3 weeks prior to first dose of study treatment. An exception for the washout of hormonal
therapies is gonadotropin releasing hormone agonists used for ovarian suppression in
premenopausal women, which are permitted concomitant medications
5. Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the
following exceptions:
● Alopecia;
● Neuropathy, which must have resolved to ≤ Grade 2;
● Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the
time of occurrence, and must have resolved completely
6. Clinically significant cardiopulmonary disease such as:
● Ventricular arrhythmia requiring therapy
● Symptomatic hypertension or uncontrolled asymptomatic hypertension as determined
by the investigator
● Any history of symptomatic CHF, symptomatic left ventricular systolic dysfunction
or symptomatic decrease in ejection fraction
● Severe dyspnea at rest (Common Terminology Criteria for Adverse Events [CTCAE]
Grade 3 or above) due to complications of advanced malignancy or hypoxia requiring
supplementary oxygen therapy
● ≥ Grade 2 QTc prolongation on screening electrocardiogram (ECG)
7. Known myocardial infarction or unstable angina within 6 months prior to first dose of
study treatment
8. Known carrier of Hepatitis B or Hepatitis C or has other known chronic liver disease
9. Subjects known to be positive for human immunodeficiency virus (HIV) if they meet any
of the following criteria:
● CD4+ T-cell count of <350 cells/uL
● Detectable HIV viral load
● History of an opportunistic infection within the past 12 months
● On stable antiretroviral therapy for <4 weeks
10. Subjects who are pregnant, breastfeeding, or planning to become pregnant from time of
informed consent until 7 months following the last dose of study drug
11. Unable to swallow pills or has significant gastrointestinal disease which would preclude
the adequate oral absorption of medications
12. Use of a strong CYP3A4 or CYP2C8 inhibitor within 1 week, or use of a strong CYP3A4
or CYP2C8 inducer within 5 days prior to the first dose of study treatment (see Appendix
C and Appendix D). CYP3A4 or CYP2C8 inducers and inhibitors are also prohibited as
concomitant medications within 1 week of discontinuation of tucatinib treatment. Use of
sensitive CYP3A substrates (Appendix E:) should be avoided 1 week before enrollment
and during study treatment.
13. Unable to undergo contrast MRI of the brain
14. Other medical, social, or psychosocial factors that, in the opinion of the investigator,
could impact safety or compliance with study procedures
15. Systemic therapy for another malignancy within 2 years of the start of study treatment
16. CNS Exclusion – Based on screening brain MRI, subjects must not have any of the
following:
a. Any untreated brain lesions >2.0 cm in size, unless approved by the medical monitor
b. Ongoing use of systemic corticosteroids for control of symptoms of brain metastases
at a total daily dose of >2 mg of dexamethasone (or equivalent). However, subjects on
a chronic stable dose of ≤2 mg total daily of dexamethasone (or equivalent) may be
eligible with approval of the medical monitor.
c. Any brain lesion thought to require immediate local therapy, including (but not
limited to) a lesion in an anatomic site where increase in size or possible treatmentrelated edema may pose risk to the subject (e.g., brain stem lesions). Subjects who
undergo local treatment for such lesions identified by screening contrast brain MRI
may still be eligible for the study based on criteria described under CNS
Inclusion 18c (ii).
d. Known or concurrent leptomeningeal disease as documented by the investigator
e. Poorly controlled (>1/week) generalized or complex partial seizures, or manifest
neurologic progression due to brain metastases notwithstanding CNS-directed therapy
investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with
lapatinib or neratinib within 12 months of starting study treatment (except in cases where
they were given for ≤21 days and was discontinued for reasons other than disease
progression or severe toxicity). Prior treatment with pyrotinib for recurrent or mBC
(except in cases where pyrotinib was given for ≤21 days and was discontinued for
reasons other than disease progression or severe toxicity)
Prior treatment with T-DM1 in any treatment setting
3. History of allergic reactions to trastuzumab or compounds chemically or biologically
similar to tucatinib, except for Grade 1 or 2 infusion-related reactions to trastuzumab that
were successfully managed, or known allergy to any of the excipients in the study drugs
4. Treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS
radiation, experimental agent or participation in another interventional clinical trial
≤3 weeks prior to first dose of study treatment. An exception for the washout of hormonal
therapies is gonadotropin releasing hormone agonists used for ovarian suppression in
premenopausal women, which are permitted concomitant medications
5. Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the
following exceptions:
● Alopecia;
● Neuropathy, which must have resolved to ≤ Grade 2;
● Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the
time of occurrence, and must have resolved completely
6. Clinically significant cardiopulmonary disease such as:
● Ventricular arrhythmia requiring therapy
● Symptomatic hypertension or uncontrolled asymptomatic hypertension as determined
by the investigator
● Any history of symptomatic CHF, symptomatic left ventricular systolic dysfunction
or symptomatic decrease in ejection fraction
● Severe dyspnea at rest (Common Terminology Criteria for Adverse Events [CTCAE]
Grade 3 or above) due to complications of advanced malignancy or hypoxia requiring
supplementary oxygen therapy
● ≥ Grade 2 QTc prolongation on screening electrocardiogram (ECG)
7. Known myocardial infarction or unstable angina within 6 months prior to first dose of
study treatment
8. Known carrier of Hepatitis B or Hepatitis C or has other known chronic liver disease
9. Subjects known to be positive for human immunodeficiency virus (HIV) if they meet any
of the following criteria:
● CD4+ T-cell count of <350 cells/uL
● Detectable HIV viral load
● History of an opportunistic infection within the past 12 months
● On stable antiretroviral therapy for <4 weeks
10. Subjects who are pregnant, breastfeeding, or planning to become pregnant from time of
informed consent until 7 months following the last dose of study drug
11. Unable to swallow pills or has significant gastrointestinal disease which would preclude
the adequate oral absorption of medications
12. Use of a strong CYP3A4 or CYP2C8 inhibitor within 1 week, or use of a strong CYP3A4
or CYP2C8 inducer within 5 days prior to the first dose of study treatment (see Appendix
C and Appendix D). CYP3A4 or CYP2C8 inducers and inhibitors are also prohibited as
concomitant medications within 1 week of discontinuation of tucatinib treatment. Use of
sensitive CYP3A substrates (Appendix E:) should be avoided 1 week before enrollment
and during study treatment.
13. Unable to undergo contrast MRI of the brain
14. Other medical, social, or psychosocial factors that, in the opinion of the investigator,
could impact safety or compliance with study procedures
15. Systemic therapy for another malignancy within 2 years of the start of study treatment
16. CNS Exclusion – Based on screening brain MRI, subjects must not have any of the
following:
a. Any untreated brain lesions >2.0 cm in size, unless approved by the medical monitor
b. Ongoing use of systemic corticosteroids for control of symptoms of brain metastases
at a total daily dose of >2 mg of dexamethasone (or equivalent). However, subjects on
a chronic stable dose of ≤2 mg total daily of dexamethasone (or equivalent) may be
eligible with approval of the medical monitor.
c. Any brain lesion thought to require immediate local therapy, including (but not
limited to) a lesion in an anatomic site where increase in size or possible treatmentrelated edema may pose risk to the subject (e.g., brain stem lesions). Subjects who
undergo local treatment for such lesions identified by screening contrast brain MRI
may still be eligible for the study based on criteria described under CNS
Inclusion 18c (ii).
d. Known or concurrent leptomeningeal disease as documented by the investigator
e. Poorly controlled (>1/week) generalized or complex partial seizures, or manifest
neurologic progression due to brain metastases notwithstanding CNS-directed therapy
The Estimated Number of Participants
-
Taiwan
5 participants
-
Global
570 participants
