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HER2-positive Metastatic Breast CancerPhase 3NCT06278870

Disitamab Vedotin + Pyrotinib Versus THP in the First-line Treatment for HER2+ Advanced Breast Cancer Clinical Trial

A Phase 3 study testing disitamab vedotin, Pyrotinib and trastuzumab in people with HER2-positive Metastatic Breast Cancer and First-line Treatment, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site 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
Search all trials

Trial summary

The goal of this multicentre, randomized, double-blind controlled, phase III clinical trial is to compare the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab (THP) for newly diagnosed… Read more about this study

Who is it for?
Ages 18 to 75 years, women only
What is being tested?
disitamab vedotin, Pyrotinib and trastuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
312 participants
Where
1 siteChina
Study dates
6 Sep 2023to 30 Jun 2031
Phase
Phase 3
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 to 75 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult female patients (age 18-75 years) with metastatic breast cancer confirmed by pathology or imaging;
  • Pathologically confirmed HER2 positive (definition: Immunohistochemistry(IHC) 3+, or IHC 2+ and Fluorescent In Situ Hybridization(FISH) amplification);
  • No previous chemotherapy regimen for metastatic breast cancer;
  • At least one measurable lesion exists (Response Evaluation Criteria in Solid Tumors(RECIST) 1.1);
  • Eastern Cooperative Oncology Group(ECOG) performance status score ≤ 2 and expected survival of not less than 3 months;
  • Prior treatment-related toxicity at enrollment must have resolved to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) (version 5.0) ≤ 1 degree (except for alopecia or other toxicity that, in the judgment of the investigator, is not considered a risk to the safety of the patient);
Show all 20Show fewer
  • Patients with adequate organ function before enrollment:
  • White Blood Cell (WBC) ≥ 3.0 x 10^9/L;
  • Neutrophil granulocyte (ANC) ≥1.5 x 10^9/L;
  • Platelet (PLT) ≥70×10^9/L;
  • Liver, kidney, and cardiac function tests are essentially normal (based on the normal values in the laboratory of each study center):
  • Total bilirubin (TBIL) ≤ 3 x Upper Limit of Normal (ULN);
  • Alanine aminotransferase (ALT/AST) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases);
  • serum creatinine ≤ 1.5 x ULN or creatinine clearance (Ccr) ≥ 60 ml/min;
  • . Normal cardiac function;
  • Left ventricular ejection fraction (LVEF) ≥ 55%;
  • QT-interval corrected with Fridericia (QTcF) ≤ 470ms;
  • Hormone receptor status is clear;
  • Female patients of childbearing potential who have a negative pregnancy test and agree to use an effective non-hormonal method of contraception during treatment and for at least 6 months after the last dose of the test drug;
  • Able to understand the study process, voluntarily participate in this study, and sign an informed consent form.

Who cannot join

  • Pathology suggestive of HER2 negativity (IHC 2+ and FISH-, or IHC 1+);
  • Patients with known hypersensitivity to the active ingredient or other components of the study drug;
  • Patients during pregnancy or lactation, patients with childbearing potential tested positive in a baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial;
  • Patients not eligible for this study judged by the investigator, a pre-existing disease or condition that may interfere with participation in the study or any serious medical disorder that may interfere with the safety of the subject (e.g., uncontrolled heart disease, high blood pressure, active or uncontrolled infections, active hepatitis B virus infection).

Trial locations and contacts

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

China1 site, 1 recruiting

  • Sun Yat-sen Memorial Hospital,Sun Yat-sen University

    Guangzhou, Guangdong, 510000

    Herui Yao, PhD, +86 13500018020, yaoherui@mail.sysu.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Disitamab Vedotin in Combination With Pyrotinib Versus THP in the First-line Treatment for HER2-positive Advanced Breast Cancer, a Multicentre, Randomized, Double-blind Controlled, Phase III Trial

The goal of this multicentre, randomized, double-blind controlled, phase III clinical trial is to compare the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab (THP) for newly diagnosed recurrent/metastatic Human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer, and to explore the impact of biomarkers on clinical efficacy and safety. The main questions it aims to answer are:

  • Analyse the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of THP.
  • Explore the impact of biomarkers on clinical efficacy and safety of the combination of disitamab vedotin in combination with pyrotinib treatment.
Read more

Participants in the experimental group will receive disitamab vedotin in combination with pyrotinib for 6-8 cycles (each cycle lasting 28 days), followed by maintenance treatment with trastuzumab in combination with pyrotinib. Participants in the control group will receive paclitaxel in combination with trastuzumab and pertuzumab for 6-8 cycles (each cycle lasting 21 days), followed by maintenance treatment with trastuzumab and pertuzumab.

Researchers will compare disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab to see if disitamab vedotin in combination with pyrotinib could be a new option for first-line treatment of HER2-positive metastatic breast cancer.

Being tested
disitamab vedotin, Pyrotinib, trastuzumab, Pertuzumab, taxane drug

What participants receive

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

  • disitamab vedotinDrug

    Also called RC-48

    disitamab vedotin 2mg/kg iv q2w

  • PyrotinibDrug

    pyrotinib 400mg po q28d

  • trastuzumabDrug

    trastuzumab 8mg/kg for the first cycle, 6mg/kg for subsequent treatments iv q21d

  • PertuzumabDrug

    pertuzumab 840mg for the first cycle, 420mg for subsequent treatments iv q21d

  • taxane drugDrug

    Docetaxel/paclitaxel/albumin paclitaxel/liposomal paclitaxel, dosage and administration are determined according to the latest version of the NCCN and CSCO breast cancer guideline recommendations

Study groups in NCT06278870
Study groupRoleWhat they receive
disitamab vedotin in combination with pyrotinibExperimentaldisitamab vedotin 2mg/kg IV every 14 days + Pyrotinib 400mg PO daily, with each 28-day cycle. After 6-8 cycles, adding Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pyrotinib 400mg PO daily for maintenance.
Receives: Drug: disitamab vedotin; Drug: Pyrotinib; Drug: trastuzumab
taxane drug in combination with trastuzumab and pertuzumabActive comparatortaxane drug (Docetaxel/Paclitaxel/Albumin Paclitaxel/Liposomal Paclitaxel, dosing and administration per latest National Comprehensive Cancer Network(NCCN) and Chinese Society of Clinical Oncology(CSCO) breast cancer guidelines) + Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pertuzumab initially at 840mg IV followed by 420mg IV every 21 days, with each 21-day cycle. After 6-8 cycles, continuing with Trastuzumab at 6mg/kg IV every 21 days + Pertuzumab at 420mg IV every 21 days for maintenance.
Receives: Drug: trastuzumab; Drug: Pertuzumab; Drug: taxane drug

What is being measured

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

  1. Progression Free Survival (PFS)

    From enrollment to progression or death (for any reason)

    Measured: Estimated 30 months

Secondary outcomes (7)

  1. Overall Survival (OS)

    From enrollment to death (for any reason)

    Measured: Estimated 8 years

  2. Disease control rate (DCR)

    Ratio of complete response (CR) , partial response (PR) and stable disease (SD) in all subjects

    Measured: Estimated 30 months

  3. Objective Response Rate (ORR)

    Ratio of CR and PR in all subjects

    Measured: Estimated 30 months

  4. Clinical Benefit rate (CBR)

    Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects

    Measured: Estimated 30 months

  5. Adverse Events (Based on CTCAE 5.0 standards)

    Safety

    Measured: From informed consent through 28 days following treatment completion

  6. Quality of Life (QoL) by Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B)

    QoL was assessed using FACT-B. FACT-B is a 37-item questionnaire with 5 subscales assessing physical, social, emotional, and functional well-being, with scores ranging from 0 to 4 for each question. Higher scores generally indicating a better quality of life.

    Measured: Estimated 30 months

  7. Exploration of biomarkers

    Next Generation Gene Sequencing (NGS) detection of tissue and blood specimens, including ERBB1/ERBB2/ERBB3/ERBB4/AKT/TP53/PIK3CA and so on. Objective to explore the correlation between biomarkers and the objective response rate (ORR), as well as progression-free survival (PFS).

    Measured: Estimated 30 months

Timeline

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

  1. First posted26 Feb 2024
  2. Study start6 Sep 2023
  3. Primary completion30 Jun 2031 (estimated)
  4. Study completion30 Jun 2031 (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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
312 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06278870
Sponsor's protocol ID
SYSKY-2023-431-02
Status last verified
Feb 2024
First submitted
7 Aug 2023
Last updated
26 Feb 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Koleva-Kolarova RG, Oktora MP, Robijn AL, Greuter MJW, Reyners AKL, Buskens E, de Bock GH. Increased life expectancy as a result of non-hormonal targeted therapies for HER2 or hormone receptor positive metastatic breast cancer: A systematic review and meta-analysis. Cancer Treat Rev. 2017 Apr;55:16-25. doi: 10.1016/j.ctrv.2017.01.001. Epub 2017 Feb 20.

    PubMed 28288388

  • Mendes D, Alves C, Afonso N, Cardoso F, Passos-Coelho JL, Costa L, Andrade S, Batel-Marques F. The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer--a systematic review. Breast Cancer Res. 2015 Nov 17;17:140. doi: 10.1186/s13058-015-0648-2.

    PubMed 26578067

  • Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, Bilous M, Ellis IO, Fitzgibbons P, Hanna W, Jenkins RB, Press MF, Spears PA, Vance GH, Viale G, McShane LM, Dowsett M. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018 Jul 10;36(20):2105-2122. doi: 10.1200/JCO.2018.77.8738. Epub 2018 May 30.

    PubMed 29846122

  • Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortes J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. doi: 10.1016/S1470-2045(19)30863-0. Epub 2020 Mar 12.

    PubMed 32171426

  • Glockner S, Buurman H, Kleeberger W, Lehmann U, Kreipe H. Marked intratumoral heterogeneity of c-myc and cyclinD1 but not of c-erbB2 amplification in breast cancer. Lab Invest. 2002 Oct;82(10):1419-26. doi: 10.1097/01.lab.0000032371.16521.40.

    PubMed 12379776

  • Shin SJ, Hyjek E, Early E, Knowles DM. Intratumoral heterogeneity of her-2/neu in invasive mammary carcinomas using fluorescence in-situ hybridization and tissue microarray. Int J Surg Pathol. 2006 Oct;14(4):279-84. doi: 10.1177/1066896906293055.

    PubMed 17041191

  • Brunelli M, Manfrin E, Martignoni G, Miller K, Remo A, Reghellin D, Bersani S, Gobbo S, Eccher A, Chilosi M, Bonetti F. Genotypic intratumoral heterogeneity in breast carcinoma with HER2/neu amplification: evaluation according to ASCO/CAP criteria. Am J Clin Pathol. 2009 May;131(5):678-82. doi: 10.1309/AJCP09VUTZWZXBMJ.

    PubMed 19369627

  • Cortes J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. doi: 10.1056/NEJMoa2115022.

    PubMed 35320644

  • Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. doi: 10.1056/NEJMoa2203690. Epub 2022 Jun 5.

    PubMed 35665782

  • Yao X, Jiang J, Wang X, Huang C, Li D, Xie K, Xu Q, Li H, Li Z, Lou L, Fang J. A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity. Breast Cancer Res Treat. 2015 Aug;153(1):123-33. doi: 10.1007/s10549-015-3503-3. Epub 2015 Aug 8.

    PubMed 26253944

  • Ocana A, Amir E, Pandiella A. HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates. Breast Cancer Res. 2020 Jan 31;22(1):15. doi: 10.1186/s13058-020-1252-7.

    PubMed 32005279

  • Rios-Doria J, Harper J, Rothstein R, Wetzel L, Chesebrough J, Marrero A, Chen C, Strout P, Mulgrew K, McGlinchey K, Fleming R, Bezabeh B, Meekin J, Stewart D, Kennedy M, Martin P, Buchanan A, Dimasi N, Michelotti E, Hollingsworth R. Antibody-Drug Conjugates Bearing Pyrrolobenzodiazepine or Tubulysin Payloads Are Immunomodulatory and Synergize with Multiple Immunotherapies. Cancer Res. 2017 May 15;77(10):2686-2698. doi: 10.1158/0008-5472.CAN-16-2854. Epub 2017 Mar 10.

    PubMed 28283653

  • Li BT, Michelini F, Misale S, Cocco E, Baldino L, Cai Y, Shifman S, Tu HY, Myers ML, Xu C, Mattar M, Khodos I, Little M, Qeriqi B, Weitsman G, Wilhem CJ, Lalani AS, Diala I, Freedman RA, Lin NU, Solit DB, Berger MF, Barber PR, Ng T, Offin M, Isbell JM, Jones DR, Yu HA, Thyparambil S, Liao WL, Bhalkikar A, Cecchi F, Hyman DM, Lewis JS, Buonocore DJ, Ho AL, Makker V, Reis-Filho JS, Razavi P, Arcila ME, Kris MG, Poirier JT, Shen R, Tsurutani J, Ulaner GA, de Stanchina E, Rosen N, Rudin CM, Scaltriti M. HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers. Cancer Discov. 2020 May;10(5):674-687. doi: 10.1158/2159-8290.CD-20-0215. Epub 2020 Mar 25.

    PubMed 32213539

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing disitamab vedotin, Pyrotinib and trastuzumab in people with HER2-positive Metastatic Breast Cancer and First-line Treatment, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site 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 20 inclusion and 4 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 26 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: Estimated 30 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06278870, which also lists 13 linked publications.

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 26 Feb 2024.

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