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Breast CancerPhase 2NCT06227117

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

A Phase 2 study testing Disitamab Vedotin Injection (18 weeks), Toripalimab (18weeks) and Carboplatin in people with Breast Cancer, run by RemeGen Co., Ltd. at 5 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Disitamab Vedotin Injection (18 weeks), Toripalimab (18weeks) and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
5 sitesChina
Study dates
27 Jul 2023to Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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;
  • International Normalised Ratio (INR) and Activated Fractional Thromboplastin Time ≤ 1.5 × ULN;
  • Creatinine Clearance (CrCl) ≥ 60 mL/min according to the Cockcroft-Gault formula method;
  • Female 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 .
  • 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 .
  • 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
  • Male subjects of fertile potential who meet the following criteria:
  • 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.
  • 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.
  • 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.
  • Be able to understand the requirements of the trial and be willing and able to comply with the trial and follow up procedural arrangements.

Who cannot join

  • 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
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  • 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.
  • Hypersensitivity reactions or delayed hypersensitivity reactions to components of Disitamab Vedotin and Toripalimab or analogues are known;
  • Known hypersensitivity or delayed hypersensitivity to epirubicin, cyclophosphamide, carboplatin preparations or components or similar drugs;
  • 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);

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

5 sites in 1 country

China5 sites, 5 recruiting
  • Xiangya Hospital Central South University

    Changsha, Hunan, 410008

    Juan Huang, M.D

    Not yet recruiting
  • Hunan Cancer Hospital

    Changsha, Hunan, 410031

    Quzhang Ouyang, M.D

    Not yet recruiting
  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310005

    Yang Yu, M.D

    Not yet recruiting
  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality

    Zhimin Shao, M.D.

    Recruiting
  • Tianjin Medical University Cancer Institute & Hospital

    Tianjin, Tianjin Municipality, 300060

    Jin Zhang, M.D

    Not yet recruiting

Other trials in China

About this study

Official title: A Randomized, Multicenter, Open-Label Phase II Neoadjuvant Study to Evaluate the Safety and Efficacy of Disitamab Vedotin in Combination Toripalimab or Sequence Chemotherapy in Participants With HR-negative, HER2 Low-expressing Breast Cancer

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

Read the 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.

Conditions
Breast Cancer
Being tested
Disitamab Vedotin Injection (18 weeks), Toripalimab (18weeks), Carboplatin, Disitamab Vedotin Injection (12 weeks), Sequential Epirubicin
Keywords
Breast Cancer, HR-negative, HER2 low-expressing
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Disitamab Vedotin Injection (18 weeks)Drug

    Also called DV,RC48-ADC

    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.

  • Toripalimab (18weeks)Drug

    Also called JS001

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

  • CarboplatinDrug

    AUC 3 Q2W or AUC1.5 QW intravenous infusion

  • Disitamab Vedotin Injection (12 weeks)Drug

    Also called DV,RC48-ADC

    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.

  • Sequential EpirubicinDrug

    Also called Epirubicin

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

  • Sequential CTXDrug

    Also called CTX, cyclophosphamide

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

  • Toripalimab (12weeks)Drug

    Also called JS001

    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.

Study groups in NCT06227117
Study groupRoleWhat they receive
Disitamab Vedotin + ToripalimabExperimentalDisitamab Vedotin with Toripalimab Arm
Receives: Drug: Disitamab Vedotin Injection (18 weeks); Drug: Toripalimab (18weeks)
Disitamab Vedotin + Toripalimab+CarboplatinExperimentalDisitamab Vedotin + Toripalimab with Carboplatin Arm
Receives: Drug: Disitamab Vedotin Injection (18 weeks); Drug: Toripalimab (18weeks); Drug: Carboplatin
Disitamab Vedotin + Toripalimab sequential Epirubicin+ CTX+ ToripalimabExperimentalDisitamab Vedotin + Toripalimab sequential Epirubicin+ CTX with Toripalimab Arm
Receives: Drug: Disitamab Vedotin Injection (12 weeks); Drug: Sequential Epirubicin; Drug: Sequential CTX; Drug: Toripalimab (12weeks)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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;

    Measured: 1 month after surgery

Secondary outcomes (11)
  1. Breast pathological complete response(bpCR)

    Defined as the proportion of participants with a pathological assessment of bpCR in the analyzed population

    Measured: 1 month after surgery

  2. Objective remission rate (ORR)

    Objective response rate.ORR assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST 1.1)

    Measured: Baseline to surgery

  3. Disease free survival(DFS)

    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

    Measured: Up to approximately 3 or 5 years

  4. Event free survival (EFS)

    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;

    Measured: Up to approximately 3 or 5 years

  5. Overall survival (OS)

    OS is defined as the time from the date of randomisation until the date of death due to any cause.

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

  6. Adverse events

    To evaluate safety including adverse event rate and adverse event grade

    Measured: Up to approximately 2 months after surgery

  7. Change in cluster of differentiation 8 (CD8)

    CD8 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining.

    Measured: At baseline to surgery

  8. Health-related quality of life - EORTC-QLQ-C30

    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

    Measured: Up to approximately 2 years

  9. Residual cancer burden score

    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).

    Measured: 1 month after surgery

  10. Change in tumor-infiltrating lymphocytes (TILs)

    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.

    Measured: At baseline to surgery

  11. Change in programmed cell death protein L1 (PD-L1)

    PD1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining.

    Measured: At baseline to surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2024
  2. Study start27 Jul 2023
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06227117
Sponsor's protocol ID
RC48-C024
Status last verified
Jan 2024
First submitted
17 Jan 2024
Last updated
19 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Disitamab Vedotin Injection (18 weeks), Toripalimab (18weeks) and Carboplatin in people with Breast Cancer, run by RemeGen Co., Ltd. at 5 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Changling Li (+8610-58075763, changling.li@remegen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total pathological complete response (tpCR) rate (ypT0/Tis ypN0) (time frame: 1 month after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2024.

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