Trial Title:
Neoadjuvant Study of DV in Combination Toripalimab or Sequence Chemotherapy in HR-negative, HER2 Low-expressing Breast Cancer
NCT ID:
NCT06227117
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Cyclophosphamide
Carboplatin
Epirubicin
Disitamab vedotin
Conditions: Keywords:
Breast Cancer
HR-negative
HER2 low-expressing
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Disitamab Vedotin Injection （18 weeks）
Description:
2.0mg/kg, intravenous infusion，D1, every 2 weeks, Every 6 weeks is a treatment cycle. A
total of 3 cycles (18 weeks) of treatment are performed.
Arm group label:
Disitamab Vedotin + Toripalimab
Arm group label:
Disitamab Vedotin + Toripalimab+Carboplatin
Other name:
DV,RC48-ADC
Intervention type:
Drug
Intervention name:
Toripalimab （18weeks）
Description:
3.0 mg/kg, intravenous infusion, D1, every 2 weeks
Arm group label:
Disitamab Vedotin + Toripalimab
Arm group label:
Disitamab Vedotin + Toripalimab+Carboplatin
Other name:
JS001
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
AUC 3 Q2W or AUC1.5 QW intravenous infusion
Arm group label:
Disitamab Vedotin + Toripalimab+Carboplatin
Intervention type:
Drug
Intervention name:
Disitamab Vedotin Injection （12 weeks）
Description:
2.0mg/kg, intravenous infusion，D1, every 2 weeks, Every 6 weeks is a treatment cycle. A
total of 2 cycles (12 weeks) of treatment are performed.
Arm group label:
Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ Toripalimab
Other name:
DV,RC48-ADC
Intervention type:
Drug
Intervention name:
Sequential Epirubicin
Description:
According to body surface area, 90mg/m2, intravenous infusion, D1, every 3 weeks, A total
of 12 weeks of treatment are performed.
Arm group label:
Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ Toripalimab
Other name:
Epirubicin
Intervention type:
Drug
Intervention name:
Sequential CTX
Description:
According to body surface area,600mg/m2, intravenous infusion, D1, every 3 weeks, A total
of 12 weeks of treatment are performed.
Arm group label:
Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ Toripalimab
Other name:
CTX, cyclophosphamide
Intervention type:
Drug
Intervention name:
Toripalimab （12weeks）
Description:
3.0 mg/kg, intravenous infusion, D1, every 2 weeks, A total of 2 cycles (12 weeks) of
treatment are performed. Sequential therapy 3.0 mg/kg, intravenous infusion, D1, every 2
weeks, A total of 2 cycles (12 weeks) of treatment are performed.
Arm group label:
Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ Toripalimab
Other name:
JS001
Summary:
The purpose of this study is to evaluate the Safety and Efficacy of Neoadjuvant study of
DV in combination Toripalimab i or sequence chemotherapy in HR-negative, HER2
low-expressing Breast Cancer
Detailed description:
This is an open-label, randomized, multicenter, Phase II Neoadjuvant Therapy Study
designed to evaluate the Safety and Efficacy of Neoadjuvant study of DV in combination
Toripalimab or sequence chemotherapy in HR-negative, HER2 low-expressing Breast Cancer
The primary objectives of the study are to explore combination neoadjuvant therapy in
participants with previously untreated HR-negative, HER2 low-expressing breast cancer, by
assessment of tpCR and EFS.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily participate and sign the informed consent form;
2. Ages≥18 years;
3. Invasive breast tumour tissue with low HER2 expression confirmed by the central
laboratory, defined as HER2 protein expression of IHC 1+ or IHC 2+ with no
amplification by in situ hybridisation (ISH) (according to the Breast Cancer HER2
Detection Guidelines, 2019 edition) by immunohistochemistry; and specimens from the
primary site of the tumour for HER2 detection (wax blocks, biopsies, or fresh
tissues are acceptable) are available for HER2 detection
4. Tumour hormone receptor (HR)-negative, defined as IHC-stained invasive carcinoma
with a proportion of cells positive for both ER and PgR nuclear staining of <1%
according to ASCO/CAP guideline 2020;
5. Histologically confirmed invasive carcinoma of the breast according to AJCC 8th
edition investigator-assessed clinical staging T1cN1-2M0, or T2-3N0-2M0
6. Subjects who tolerate and are scheduled to undergo radical breast cancer surgery and
have not received any prior anti-tumour systemic therapy for breast cancer, as
assessed by the research centre;
7. ECOG PS 0 or 1 point
8. At least one measurable lesion according to RECIST v1.1 criteria;
9. Cardiac function: New York Heart Association (NYHA) class <3; left ventricular
ejection fraction ≥55%;
10. Bone marrow or organ function, the following criteria should be met within 7 days
prior to study dosing (normal values are based on the clinical trial centre, no
transfusion of blood, haematopoietic stimulating factors, albumin or blood products
within 14 days prior to the test):
1. haemoglobin ≥ 90 g/L;
2. absolute neutrophil count (ANC) ≥ 1.5 × 109 /L;
3. platelets ≥ 100 × 109 /L;
4. serum total bilirubin ≤ 1.5 times the Upper Limit of Normal (ULN);
5. Albuminous Transaminase (AST) and Albuminous Transaminase (ALT) ≤ 2.5 × ULN;
6. International Normalised Ratio (INR) and Activated Fractional Thromboplastin
Time ≤ 1.5 × ULN;
7. Creatinine Clearance (CrCl) ≥ 60 mL/min according to the Cockcroft-Gault
formula method;
11. Female subjects of childbearing potential who meet the following criteria:
1. A serum pregnancy test (minimum sensitivity of 25 mIU/mL or equivalent units of
β-human chorionic gonadotropin [β-hCG]) must be negative within 72 hours prior
to the first dose of study intervention. Subjects with false-positive results
and confirmed non-pregnancy will be eligible for participation in the study.
2. Must agree to contraception for the duration of the study and for at least 6
months after the last dose of study drug .
3. Must agree not to breastfeed or donate eggs from the time of signing the
informed consent until 6 months after the last dose of study drug .
4. If sexually active and likely to result in pregnancy, use of at least 2
acceptable contraceptive methods, at least 1 of which must be highly effective,
must be continued from the time of informed consent for at least 6 months after
the last dose of study drug
12. Male subjects of fertile potential who meet the following criteria:
1. It is necessary to agree not to donate sperm from the time of signing the
informed consent form until at least 4 months after the last dose of study
drug.
2. If sexual intercourse with a person of childbearing potential is likely to
result in pregnancy, continuous use of at least 2 acceptable contraceptives, at
least 1 of which must be highly effective, beginning at the time of informed
consent and continuing until at least 4 months after the last dose of study
drug. Beginning at the time of informed consent and continuing for at least 4
months after the last dose of study drug.
3. If sex with a pregnant or breastfeeding patient, condom use must be continuous
from the time of informed consent and continue until at least 4 months after
the last dose of study drug.
13. Be able to understand the requirements of the trial and be willing and able to
comply with the trial and follow up procedural arrangements.
Exclusion Criteria:
1. With bilateral invasive breast cancer
2. Previous history of invasive breast cancer
3. Previous carcinoma in situ of the breast with adjuvant endocrine therapy within 5
years of surgery
4. Use of investigational drugs or major surgery within 4 weeks prior to start of study
drug administration
5. Live or live attenuated vaccine administered within 4 weeks prior to the start of
study drug administration or planned to be administered during the study period
6. History of previous allogeneic haematopoietic stem cell transplantation or organ
transplantation
7. Prior treatment with PD-(L)1, PD-L2, CTLA4 inhibitors and other antibody-coupled
drugs;
8. Uncontrolled or significant cardiovascular disease, including (but not limited to):
any of the following within 6 months prior to the first dose: e.g., congestive heart
failure (NYHA class III or IV), myocardial infarction or cerebral infarction (except
for lacunar cerebral infarction), pulmonary embolism, unstable angina, or arrhythmia
requiring treatment at screening; primary cardiomyopathy (e.g., dilated
cardiomyopathy, Primary cardiomyopathies (e.g., dilated cardiomyopathy, hypertrophic
cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive
cardiomyopathy, indeterminate cardiomyopathy); history of clinically significant
prolongation of the QTc period, grade II type II AV block or grade III AV block or
QTc interval (F method) >470 msec (women) or >450 msec (men); atrial fibrillation
(EHRA grade ≥2b); uncontrolled hypertension that is judged by the investigator to be
unsuitable; and Hypertension, judged by the investigator to be unsuitable for
participation in the study;
9. History of interstitial lung disease requiring treatment or current severe lung
disease including, but not limited to, active tuberculosis, interstitial lung
disease;
10. Ongoing active infection that requires systemic treatment;
11. Have an active autoimmune disease requiring systemic treatment within the past 2
years (e.g., use of corticosteroids or immunosuppressive drugs, etc.), allowing for
relevant replacement therapy (e.g., thyroxine, insulin, or physiological
corticosteroid replacement therapy for adrenal or pituitary insufficiency)
12. A clear past or present history of a neurological or psychiatric disorder, including
epilepsy or dementia
13. Ongoing grade ≥2 sensory or motor neuropathy;
14. Concomitant disease that, in the investigator's judgement, is a serious hazard to
the subject's safety or interferes with the subject's ability to complete the
clinical study;
15. Positive HIV test results; patients with active hepatitis B or C (HBsAg positivity
accompanied by HBV DNA titres above the upper limit of normal; HCVAb positivity
accompanied by HCV RNA titres above the upper limit of normal); and persistent
coronavirus (COVID-19) infection.
16. Hypersensitivity reactions or delayed hypersensitivity reactions to components of
Disitamab Vedotin and Toripalimab or analogues are known;
17. Known hypersensitivity or delayed hypersensitivity to epirubicin, cyclophosphamide,
carboplatin preparations or components or similar drugs;
18. Other malignancy within 5 years prior to signing the informed consent (except for
non-melanoma skin cancer, cervical carcinoma in situ or other tumours that have been
effectively treated and are considered cured);
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Xiangya Hospital Central South University
Address:
City:
Changsha
Zip:
410008
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Juan Huang, M.D
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Zip:
410031
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Quzhang Ouyang, M.D
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhimin Shao, M.D.
Facility:
Name:
Tianjin Medical University Cancer Institute & Hospital
Address:
City:
Tianjin
Zip:
300060
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jin Zhang, M.D
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Zip:
310005
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yang Yu, M.D
Start date:
July 27, 2023
Completion date:
December 2026
Lead sponsor:
Agency:
RemeGen Co., Ltd.
Agency class:
Industry
Source:
RemeGen Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06227117
