Neoadjuvant Study of DV in Combination Toripalimab or Sequence Chemotherapy in HR-negative, HER2 Low-expressing Breast Cancer

NCT06227117 | Recruiting Phase 2

• 1 other identifier: RC48-C024
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 5

Brief 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

Conditions

Breast Cancer

Keywords

Breast Cancer; HR-negative; HER2 low-expressing

Outcome Measures

Primary Outcomes (1)

• Total pathological complete response (tpCR) rate (ypT0/Tis ypN0)

  Defined as the proportion of participants with a pathological assessment of pCR (ypTO/Tis, ypNO) in the analyzed population;

  1 month after surgery

Secondary Outcomes (11)

• Breast pathological complete response（bpCR）

  1 month after surgery

• Objective remission rate (ORR)

  Baseline to surgery

• Disease free survival（DFS）

  Up to approximately 3 or 5 years

• Event free survival (EFS)

  Up to approximately 3 or 5 years

• Overall survival (OS)

  Date of randomization to date of death due to any cause, up to 5 years after the last subject randomized

Study Arms (3)

Disitamab Vedotin + Toripalimab

EXPERIMENTAL

Disitamab Vedotin with Toripalimab Arm

Drug: Disitamab Vedotin Injection （18 weeks）; Drug: Toripalimab （18weeks）

Disitamab Vedotin + Toripalimab+Carboplatin

EXPERIMENTAL

Disitamab Vedotin + Toripalimab with Carboplatin Arm

Drug: Disitamab Vedotin Injection （18 weeks）; Drug: Toripalimab （18weeks）; Drug: Carboplatin

Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ Toripalimab

EXPERIMENTAL

Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX with Toripalimab Arm

Drug: Disitamab Vedotin Injection （12 weeks）; Drug: Sequential Epirubicin; Drug: Sequential CTX; Drug: Toripalimab （12weeks）

Interventions

Disitamab Vedotin Injection （18 weeks） DRUG

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.

Also known as: DV,RC48-ADC

Disitamab Vedotin + Toripalimab; Disitamab Vedotin + Toripalimab+Carboplatin

Toripalimab （18weeks） DRUG

3.0 mg/kg, intravenous infusion, D1, every 2 weeks

Also known as: JS001

Disitamab Vedotin + Toripalimab; Disitamab Vedotin + Toripalimab+Carboplatin

Carboplatin DRUG

AUC 3 Q2W or AUC1.5 QW intravenous infusion

Disitamab Vedotin + Toripalimab+Carboplatin

Disitamab Vedotin Injection （12 weeks） DRUG

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.

Also known as: DV,RC48-ADC

Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ Toripalimab

Sequential Epirubicin DRUG

According to body surface area, 90mg/m2, intravenous infusion, D1, every 3 weeks, A total of 12 weeks of treatment are performed.

Also known as: Epirubicin

Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ Toripalimab

Sequential CTX DRUG

According to body surface area,600mg/m2, intravenous infusion, D1, every 3 weeks, A total of 12 weeks of treatment are performed.

Also known as: CTX, cyclophosphamide

Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ Toripalimab

Toripalimab （12weeks） DRUG

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.

Also known as: JS001

Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ Toripalimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate and sign the informed consent form;
• Ages≥18 years;
• 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
• 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;
• Histologically confirmed invasive carcinoma of the breast according to AJCC 8th edition investigator-assessed clinical staging T1cN1-2M0, or T2-3N0-2M0
• 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;
• ECOG PS 0 or 1 point
• 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;

You may not qualify if:

• 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
• Use of investigational drugs or major surgery within 4 weeks prior to start of study drug administration
• 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
• History of previous allogeneic haematopoietic stem cell transplantation or organ transplantation
• Prior treatment with PD-(L)1, PD-L2, CTLA4 inhibitors and other antibody-coupled drugs;
• 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;
• Ongoing active infection that requires systemic treatment;
• 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)
• A clear past or present history of a neurological or psychiatric disorder, including epilepsy or dementia
• Ongoing grade ≥2 sensory or motor neuropathy;
• 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;
• 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.

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (5)

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

NOT YET RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

NOT YET RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310005, China

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carboplatin; Epirubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Changling Li

  RemeGen Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Changling Li

CONTACT

+8610-58075763; changling.li@remegen.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: January 26, 2024
• Study Start: July 27, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)