- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06178159
DV in Combination With Pertuzumab With or Without Toripalimab Neoadjuvant Therapy With HER2-positive Breast Cancer
A Phase II, Multicenter, Open-Label Neoadjuvant Study to Evaluate the Safety and Efficacy of Disitamab Vedotin in Combination With Pertuzumab With or Without Toripalimab for HER2 Positive Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is an open-label, randomized, multicenter, Phase II Study designed to evaluate safety and efficacy of Disitamab Vedotin in combination with Pertuzumab with or without Toripalimab neoadjuvant therapy inr patients with HER2-positive breast cancer.
The primary objectives of the study are to explore combination neoadjuvant therapy in participants with previously untreated HER2-positive breast cancer, by assessment of pCR .
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jianmin Fang, Ph.D
- Phone Number: +8610-58075763
- Email: Jianminfang@hotmail.com
Study Locations
-
-
Shanghai
-
Shanghai, Shanghai, China, 200433
- Recruiting
- Fudan University Shanghai Cancer Center
-
Contact:
- Jiong Wu, Ph.D
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Voluntarily participate and sign the informed consent form;
- Ages≥18 years;
- Histopathologically confirmed invasive breast cancer, clinical stage T2-3 (tumor diameter > 2 cm), cN0- 3, M0;
- Invasive breast tumour tissue confirmed HER2-positive by the central laboratory, defined as HER2 protein expression of IHC 3+ by immunohistochemistry (IHC) or IHC 2+ with amplification by in situ hybridisation (ISH) (according to the HER2 Guidelines for Breast Cancer, 2019 edition); and specimens from the primary site of the tumour for HER2 testing (wax blocks, sections or fresh tissue are acceptable) can be provided for HER2 testing;
- 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 site.
- At least one measurable lesion according to RECIST v1.1 criteria;
- Cardiac function: New York Heart Association (NYHA) class <3; left ventricular ejection fraction ≥55%;
- 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): haemoglobin ≥ 90 g/L; absolute neutrophil count (ANC) ≥ 1.5 × 109 /L; platelets ≥ 100 × 109 /L; serum total bilirubin ≤ 1.5 times the Upper Limit of Normal (ULN); Albuminous Transaminase (AST) and Albuminous Transaminase (ALT) ≤ 2.5 × ULN; International Normalised Ratio (INR) and Activated Fractional Thromboplastin Time ≤ 1.5 × ULN; and Creatinine Clearance (CrCl) ≥ 50 mL/min according to the Cockcroft-Gault formula method;
Subjects of childbearing potential who meet the following criteria:
- 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.
- Must agree to contraception for the duration of the study and for at least 6 months after the last dose of study drug (7 months after the last dose of patulizumab).
- 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 (7 months after the last dose of patulizumab).
- 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 (7 months after the last dose of patulizumab).
Subjects of childbearing potential who meet the following criteria:
- Must agree not to donate sperm from the time of signing the informed consent until at least 4 months after the last dose of study drug (7 months after the last dose of patulizumab).
- If sexual intercourse with a person of childbearing potential is likely to result in pregnancy, the use of at least 2 acceptable forms of contraception, at least 1 of which must be highly effective, must be continuous, beginning at the time of informed consent and continuing until at least 4 months after the last dose of study drug (7 months after the last dose of patuximab).
- If sex with a pregnant or breastfeeding patient, condom use must be continued from the start of informed consent and continue until at least 4 months after the last dose of study drug (7 months after the last dose of patuximab).
12. 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:
- With bilateral invasive breast cancer
- Previous history of invasive breast cancer
- Previous carcinoma in situ of the breast with adjuvant endocrine therapy within 5 years of surgery
- Prior treatment with PD-(L)1, PD-L2, CTLA4 inhibitors and other antibody-coupled drugs
- Prior anti-HER2 therapy including but not limited to ADC
- Use of investigational drugs or major surgery within 4 weeks prior to start of study drug administration
- Vaccination with live or live attenuated vaccine within 4 weeks prior to the start of study drug administration or planned for the duration of the study;
- History of previous allogeneic haematopoietic stem cell transplantation or organ transplantation;
- 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;
- History of interstitial lung disease requiring treatment or current severe lung disease including, but not limited to, active tuberculosis, interstitial lung disease;
- A clear past or present history of a neurological or psychiatric disorder, including epilepsy or dementia;
- Persistent grade ≥2 sensory or motor neuropathy;
- Active infection requiring systemic therapy; active infection requiring systemic therapy ≤7 days prior to study drug administration, with routine antimicrobial prophylaxis permitted; positive HIV test results; patients with active hepatitis B or C (HBsAg positivity with HBV DNA titres above the upper limit of normal; HCVAb positivity with HCV RNA titres above the upper limit of normal); and persistent coronavirus (COVID-19) infection.
- Active autoimmune disease requiring systemic treatment within the past 2 years (e.g., use of corticosteroids or immunosuppressive drugs, etc.), allowing for related replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency);
- Other malignancy within 5 years prior to signing the Informed Consent Form (with the exception of non-melanoma skin cancer, cervical carcinoma in situ, limited prostate cancer, stage I endometrial cancer, or other tumours that have been effectively treated and are considered to have been cured);
- Hypersensitivity reactions or delayed hypersensitivity reactions to certain components of vedicilizumab, patulizumab and treprostinil or similar drugs are known;
- A concomitant disease that, in the judgement of the investigator, is a serious hazard to the safety of the subject or interferes with the subject's ability to complete the clinical study;
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Disitamab Vedotin + Pertuzumab
Disitamab Vedotin With Pertuzumab arm
|
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.
Other Names:
Initial dose 840mg, after 2nd dose 420mg intravenous infusion, every 3 weeks
|
Experimental: Disitamab Vedotin + Toripalimab+ Pertuzumab
Disitamab Vedotin+ Toripalimab with Pertuzumab arm
|
3.0 mg/kg, intravenous infusion, D1, every 2 weeks
Other Names:
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.
Other Names:
Initial dose 840mg, after 2nd dose 420mg intravenous infusion, every 3 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathological complete response (pCR) rate (ypT0/is ypN0)
Time Frame: 1 month after surgery
|
Pathological complete response rate after neoadjuvant ( both breast and axillary lymph nodes, in which the breast may have residual carcinoma in situ);
|
1 month after surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective remission rate (ORR)
Time Frame: Up to approximately 2 years
|
Objective response rate.ORR assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST 1.1)
|
Up to approximately 2 years
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Disease free survival(DFS)
Time Frame: Up to approximately 5 years
|
From the date of surgery to the first local, regional, contralateral or distant recurrence, and death from any cause including 3- and 5-year event-free survival
|
Up to approximately 5 years
|
Event free survival (EFS)
Time Frame: Up to approximately 5 years
|
The time from random assignment to disease progression, including local progression before surgery; disease recurrence-local, regional, distant, ipsilateral noninvasive, or contralateral (invasive or noninvasive)-or death from any cause;
|
Up to approximately 5 years
|
Overall survival (OS)
Time Frame: Date of randomization to date of death due to any cause, up to 5 years after the last subject randomized
|
OS is defined as the time from the date of randomisation until the date of death due to any cause.
|
Date of randomization to date of death due to any cause, up to 5 years after the last subject randomized
|
Adverse events
Time Frame: Up to approximately 2 months after surgery
|
To evaluate safety including adverse event rate and adverse event grade
|
Up to approximately 2 months after surgery
|
Change in cluster of differentiation 8 (CD8)
Time Frame: At baseline to surgery
|
CD8 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining.
|
At baseline to surgery
|
Health-related quality of life - EORTC-QLQ-C30
Time Frame: Up to approximately 2 years
|
Change from baseline in the physical functioning subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores.
Scale scores range from 0-100.
For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL.
For symptom scales, higher scores indicate greater symptom burden
|
Up to approximately 2 years
|
Residual cancer burden score
Time Frame: 1 month after surgery
|
According to the extent of the residual cancer in the primary breast cancer site (mm*mm), the residual cancer (mm*mm), cell density of residual cancer (%), proportion of carcinoma in situ (%), number of positive lymph nodes and maximum diameter of lymph node metastasis (mm), the RCB index and corresponding RCB classification can be obtained.
The RCB index and the corresponding RCB grade can be obtained based on the maximum diameter of the cancer (mm).
|
1 month after surgery
|
Change in tumor-infiltrating lymphocytes (TILs)
Time Frame: At baseline to surgery
|
Defined as infiltrating lymphocytes isolated from tumor tissue.TILs in tumor samples by biopsy right before the first neoadjuvant therapy (baseline) and by surgery immediately after surgery would be evaluated by HE or immune staining。
|
At baseline to surgery
|
Change in programmed cell death protein L1 (PD-L1)
Time Frame: At baseline to surgery
|
PD1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining.
|
At baseline to surgery
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Jianmin Fang, Ph.D, RemeGen Co., Ltd.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RC48-C026
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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