MARGetuximab Or Trastuzumab (MARGOT)

NCT04425018 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-068
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this study is to determine how well participants with stage II-III HER2-positive breast cancer respond to pre-operative treatment using one of two different combinations of drugs. Drugs and Combinations used:

• Paclitaxel, Pertzumab and Margetuximab (Margenza)
• Paclitaxel, Pertzumab and Trastuzumab (Herceptin)

Conditions

Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer; HER2-positive Breast Cancer

Keywords

Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer; HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR)

  Compare the percentage of pathologic complete response (pCR) between patients treated with neoadjuvant TMP versus THP. Subject was considered a pCR responder if they achieved RCB 0 (no residual disease at surgery) and did not receive any additional non-protocol neoadjuvant treatment. Subject was considered a pCR non-responder if they did not achieve RCB 0 (RCB I, II, or III, or did not receive surgery) or if they received additional non-protocol neoadjuvant therapy. RCB is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to 3, defined using established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer\_RCB). Higher RCB score indicates more tumor burden remaining, thus worse outcome. RCB in this trial was determined according to local pathology review.

  12 weeks

Secondary Outcomes (29)

• Rate of Pathologic Complete Response in Hormone Receptor Positive (HR+) Subjects

  12 weeks

• Rate of Pathologic Complete Response in Hormone Receptor Negative (HR-) Subjects

  12 weeks

• Residual Cancer Burden (RCB) Scores

  12 weeks

• Residual Cancer Burden (RCB) Scores in Hormone Receptor Positive (HR+) Subjects

  12 weeks

• Residual Cancer Burden (RCB) Scores in Hormone Receptor Negative (HR-) Subjects

  12 weeks

Study Arms (2)

Paclitaxel + Pertuzumab + Margetuximab

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment including laboratory evaluations, two mandatory research biopsies and follow up visits.Cycle=21 days * Paclitaxel- via IV, Day 1,8,15 of each cycle * Margetuximab via IV, Day 1 of each cycle * Pertuzumab via IV, Day 1 of each cycle

Drug: Paclitaxel; Drug: Pertuzumab; Drug: Margetuximab

Paclitaxel + Pertuzumab + Trastuzumab

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment including laboratory evaluations, two mandatory research biopsies and follow up visits.Cycle=21 days * Paclitaxel- via IV, Day 1,8,15 of each cycle * Pertuzumab via IV, Day 1 of each cycle * Trastuzumab via IV, Day 1 of each cycle

Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab

Interventions

Paclitaxel DRUG

Pre-determined dose administered via IV, Day 1,8,15 of each cycle 4 study cycles, or 12 weeks.

Also known as: Taxol, Onxal

Paclitaxel + Pertuzumab + Margetuximab; Paclitaxel + Pertuzumab + Trastuzumab

Pertuzumab DRUG

Pre-determined dose administered via IV - Day 1 of each 21- day cycle 4 study cycles, or 12 weeks.

Also known as: Perjeta

Paclitaxel + Pertuzumab + Margetuximab; Paclitaxel + Pertuzumab + Trastuzumab

Margetuximab DRUG

Pre-determined dose administered by IV - Day 1 of each 21- day cycle 4 study cycles, or 12 weeks.

Also known as: Margenza

Paclitaxel + Pertuzumab + Margetuximab

Trastuzumab DRUG

Pre-determined dose administered via IV Day 1 of each 21- day cycle for 4 study cycles, or 12 weeks.

Also known as: Herceptin, Kanjinti, Ogivri, Herzuma

Paclitaxel + Pertuzumab + Trastuzumab

Eligibility Criteria

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

You may qualify if:

• Stage II or III (according to AJCC cancer staging manual anatomic staging table, 8th edition) histologically confirmed invasive carcinoma of the breast. A minimum tumor size of 1.5 cm (in breast mass or axillary lymph node) determined by physical exam or imaging (whichever is larger) is required. Patients with inflammatory breast carcinoma (T4d) are NOT eligible.
• Centrally confirmed to have a low affinity CD16 germline genotype (FF or FV)
• HER-2 positive by 2018 American Society of Clinical Oncology/College of American Pathologists criteria, as assessed by standard institutional guidelines (central testing is not required).
• ER/PR determination is required. ER- and PR-assays should be performed by immunohistochemical methods according to standard institutional guidelines
• Bilateral breast cancers are allowed as long as both cancers are HER2-positive (as defined in 3.1.2), or the contralateral cancer is a \<1 cm, ER+ tumor.
• Patients with multifocal or multicentric disease are eligible if the treating investigator hasdetermined the patient should be treated as HER2-positive.
• Breast imaging should include dedicated ultrasound of the ipsilateral axilla. For subjects with a clinically positive axilla based on exam or imaging, a fine needle aspiration or core biopsy procedure will be performed to determine the presence of metastatic disease in the lymph nodes (though lymph node sampling procedure need not be resulted prior to patient's registration on trial, as long as all other eligibility are met).
• Men and women (with any menopausal status) ≥18 years of age are eligible.
• ECOG performance status 0 or 1
• Required laboratory values demonstrating adequate organ function:
• ANC ≥ 1000/mm3
• Hemoglobin ≥ 9 g/dl
• Platelets ≥ 100,000/mm3
• Serum creatinine \< 1.5 x ULN (institutional) OR calculated GFR ≥ 60mL/min
• Total bilirubin ≤ 1.5 x ULN (institutional). For patients with Gilbert Syndrome, the direct bilirubin should be within the institutional normal range OR total bilirubin ≤ 2.0 mg/dL.

You may not qualify if:

• Pregnant or nursing women due to the teratogenic potential of the study drugs.
• Active, unresolved infection requiring intervention
• Receipt of intravenous antibiotics for infection within 7 days prior to registration.
• Uncontrolled hypertension (systolic \>180 mm Hg and/or diastolic \>100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Class II or higher, or serious cardiac arrhythmia requiring medication.
• Significant symptoms (Grade ≥ 2) from peripheral neuropathy.
• Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes.
• Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation, or experimental therapy.
• Patients with any prior history of invasive breast cancer within the past 5 years are not eligible. Non-metastatic invasive breast cancers diagnosed more than 5 years ago and any other type of prior non-metastatic cancer is allowed.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• MacroGenics: collaborator
• Translational Breast Cancer Research Consortium: collaborator

Study Sites (14)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Brigham Cancer Center - Foxborough

Foxborough, Massachusetts, 02035, United States

Location

Dana-Farber at Milford

Milford, Massachusetts, 01757, United States

Location

Dana-Farber at South Shore Hospital

Weymouth, Massachusetts, 02190, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

UPMC Hillman Cancer Center - Arnold Palmer at Mountain View

Greensburg, Pennsylvania, 15601, United States

Location

UPMC Hillman Cancer Center - Arnold Palmer at Norwin

Irwin, Pennsylvania, 15642, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor College of Medicine Medical Center

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington Fred Hutchinson Cancer Care

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; pertuzumab; margetuximab; Trastuzumab; Ogivri

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Adrienne G. Waks, MD
• Organization: Dana-Farber Cancer Institute

adrienne_waks@dfci.harvard.edu

617-632-3800

Study Officials

• Adrienne Waks, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: June 11, 2020
• Study Start: July 13, 2020
• Primary Completion: October 24, 2024
• Study Completion (Estimated): July 1, 2027
• Last Updated: November 18, 2025
• Results First Posted: October 22, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (14)