Margetuximab vs Trastuzumab Combinations for Breast Cancer

(MARGOT Trial)

Not currently recruiting at 19 trial locations

Overseen By Adrienne Waks, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Pregnancy, Uncontrolled hypertension, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two different drug combinations to determine which is more effective for treating stage II-III HER2-positive breast cancer before surgery. One group receives paclitaxel, pertuzumab, and margetuximab (a type of targeted therapy), while the other group receives paclitaxel, pertuzumab, and trastuzumab. It targets individuals with HER2-positive breast cancer who have not received prior treatment for this condition. The trial aims to assess how well these drugs shrink the cancer before surgery. Participants must agree to undergo breast biopsies for research purposes. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you cannot have received any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, or experimental therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that margetuximab, when combined with chemotherapy, is generally safe but can cause reactions during infusion. About 13% of patients have experienced these reactions, with 1.5% being severe. While most people tolerate it well, some may have strong reactions during treatment.

In contrast, the combination of trastuzumab and pertuzumab with paclitaxel is usually well-tolerated. Studies have demonstrated impressive response rates with manageable side effects. This indicates that patients generally handle these drugs well together, with few serious issues reported.

Both drug combinations have undergone safety studies, and while some risks exist, they are generally considered safe for those who need them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about margetuximab for breast cancer because it offers a unique mechanism compared to standard treatments like trastuzumab. Margetuximab is an engineered antibody designed to enhance the immune system's ability to recognize and destroy cancer cells by engaging immune cells more effectively. This could potentially lead to improved outcomes for patients whose tumors are resistant to current HER2-targeted therapies. The combination of margetuximab with other drugs like paclitaxel and pertuzumab aims to provide a more robust attack on cancer cells, potentially enhancing treatment efficacy.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will compare two treatment combinations for HER2-positive breast cancer. One group of participants will receive margetuximab, paclitaxel, and pertuzumab. Research has shown that this combination may be effective, with 48% of patients in one study experiencing tumor shrinkage and some having confirmed positive responses. This suggests that margetuximab, when used with chemotherapy, might lead to better results than other treatments.

Another group in this trial will receive trastuzumab, paclitaxel, and pertuzumab. Studies on this combination have demonstrated significant improvements in both the time patients live without the cancer worsening and overall survival. This combination is well-documented and has a strong track record of success in treating HER2-positive breast cancer.

Both treatment combinations offer potential benefits. Trastuzumab has a proven history of improving patient outcomes, while margetuximab shows promising early results. ^{1 2 3 6 7}

Who Is on the Research Team?

Adrienne Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage II-III HER2-positive breast cancer, who haven't had invasive breast cancer in the past 5 years or any treatment for their current cancer. Participants must have proper organ function and a specific genetic profile (CD16 FF/FV). Women of childbearing age need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

Women who could become pregnant must have a negative pregnancy test within 14 days before starting treatment.

Both of my breast cancers are HER2 positive, or one is small and ER+.

My recent tests show my organs are functioning well.

Exclusion Criteria

I am currently dealing with an infection that needs treatment.

I have received treatments for my current breast cancer.

I do not have any serious diseases that could affect my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive paclitaxel, pertuzumab, and either margetuximab or trastuzumab for 12 weeks prior to surgery

12 weeks

3 visits per cycle (in-person)

Surgery

Participants undergo surgery after the 12-week treatment phase

Follow-up

Participants are monitored for safety and effectiveness after surgery

10 years

Open-label extension (optional)

Participants who respond well to margetuximab may continue to receive it for a total of one year

Additional 40 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Margetuximab
• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview The MARGOT study tests how well patients respond to pre-surgery drug combinations: Paclitaxel with Pertuzumab plus either Margetuximab or Trastuzumab. The goal is to compare these two regimens' effectiveness in treating early-stage HER2-positive breast cancer.

How Is the Trial Designed?

Group I: Paclitaxel + Pertuzumab + Trastuzumab Experimental Treatment 3 Interventions

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

Group II: Paclitaxel + Pertuzumab + Margetuximab Experimental Treatment 3 Interventions

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

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

MacroGenics

Industry Sponsor

Trials

51

Recruited

5,400+

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Published Research Related to This Trial

In a study of 57 patients with HER2-positive breast cancer receiving neoadjuvant treatment with doxorubicin and cyclophosphamide followed by trastuzumab and pertuzumab, only 3.5% developed severe heart failure, indicating a relatively low cardiac event rate.

The study found no increased risk of cardiotoxicity from the combination of trastuzumab and pertuzumab after doxorubicin-based chemotherapy, suggesting that this treatment regimen is cardiac safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. Yu, AF., Singh, JC., Wang, R., et al.[2018]

A study involving 808 patients with HER-2 positive breast cancer showed that adding pertuzumab to trastuzumab and docetaxel significantly improved overall survival, with a 3-year survival rate increase of 10% to 15%.

While pertuzumab did not worsen cardiac toxicity in patients with low cardiovascular risk, it was associated with increased side effects such as severe diarrhea and skin disorders, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

In a study of 210 patients with ERBB2-positive metastatic breast cancer, the combination of trastuzumab and pertuzumab without chemotherapy showed a 24-month overall survival rate of 79.0%, which is comparable to 78.1% for those receiving the combination with chemotherapy.

Patients receiving the chemotherapy-free regimen had a median progression-free survival of 8.4 months, significantly shorter than the 23.3 months for those who received chemotherapy, but the absence of chemotherapy resulted in fewer adverse events and slight improvements in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Huober, J., Weder, P., Ribi, K., et al.[2023]

In a study of 152 patients with HER2-positive metastatic breast cancer, the combination of taxanes with trastuzumab and pertuzumab showed a significant progression-free survival (PFS) advantage over vinorelbine in patients with newly diagnosed metastatic disease, indicating a potential benefit for this specific group.

Overall, there was no significant difference in overall survival (OS) between the two treatment groups, suggesting that both taxanes and vinorelbine are viable options when combined with trastuzumab and pertuzumab for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study. Reinhorn, D., Kuchuk, I., Shochat, T., et al.[2021]

In a study of 55 women with HER2-positive metastatic breast cancer, the combination of trastuzumab and pertuzumab with chemotherapy resulted in a median progression-free survival (PFS) of 10 months, indicating significant efficacy in this treatment approach.

The treatment was generally safe, with common side effects including neutropenia (40%), leukopenia (34.5%), and thrombocytopenia (32.7%), but serious adverse reactions were relatively low, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab plus pertuzumab in combination with chemotherapy in metastatic HER2-positive breast cancer: a retrospective single-armed cohort study in China. Qian, Y., Peng, Y., Zhou, H., et al.[2022]

The PERUSE study, involving 1436 patients with HER2-positive locally recurrent/metastatic breast cancer, confirmed that the combination of pertuzumab and trastuzumab with taxanes (docetaxel or paclitaxel) is safe and effective, with a median overall survival of 65.3 months and a median progression-free survival of 20.7 months.

The study found that paclitaxel is a valid alternative to docetaxel as the chemotherapy backbone, and identified risk factors that could help guide future clinical trials, particularly noting that patients with hormone receptor-positive disease had better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Miles, D., Ciruelos, E., Schneeweiss, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11362812/

Expanding treatment options for patients with HER2+ ... The 5-year survivals in patients with HER2+/hormone receptor (HR) + and HER2+/HR negative (–) metastatic (M) BC are 45.6% and 39.5%, ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/18/NCT04425018/Prot_SAP_000.pdf

1 MARGetuximab Or Trastuzumab (MARGOT) This is a randomized open-label phase II trial comparing paclitaxel/margetuximab/pertuzumab. (TMP) to paclitaxel/trastuzumab/pertuzumab ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/LB1-02/752209/Abstract-LB1-02-MARGOT-TBCRC052-A-randomized-phase

Abstract LB1-02: MARGOT/TBCRC052: A randomized phase ... Margetuximab combined with chemotherapy modestly improves outcomes compared to trastuzumab plus chemotherapy in pts with heavily pre-treated HER2+ metastatic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9059982/

Profile of Margetuximab: Evidence to Date in the Targeted ... Among 24 patients with breast cancer evaluable for response, 11 (48%) experienced tumor reduction with confirmed responses in four patients (17 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04425018

NCT04425018 | MARGetuximab Or Trastuzumab (MARGOT) 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 ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02937

Margetuximab Versus Trastuzumab in Patients With ... The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ...

7. withpower.com withpower.com/trial/phase-3-breast-neoplasms-6-2020-b99f0

Margetuximab vs Trastuzumab Combinations for Breast ... Margetuximab, when combined with chemotherapy, has been associated with infusion-related reactions (IRR) in 13% of patients, with 1.5% experiencing severe ...