Margetuximab vs Trastuzumab Combinations for Breast Cancer

(MARGOT Trial)

Recruiting at 15 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

174 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Margetuximab in combination with other treatments for breast cancer?

Research shows that combining trastuzumab and pertuzumab with taxane-based chemotherapy is effective for treating HER2-positive metastatic breast cancer, improving survival rates. Pertuzumab, when added to trastuzumab and chemotherapy, has been shown to increase survival and progression-free survival without significantly increasing heart-related side effects. ^{1 2 3 4 5}

What safety data exists for Margetuximab and Trastuzumab combinations in breast cancer treatment?

Margetuximab, when combined with chemotherapy, has been associated with infusion-related reactions (IRR) in 13% of patients, with 1.5% experiencing severe reactions. Common side effects include fatigue, nausea, diarrhea, and headache. Trastuzumab and pertuzumab, used together, have limited cardiac safety data, but are generally considered safe in combination with chemotherapy for HER2-positive breast cancer. ^{4 6 7 8 9}

How is the drug combination of Margetuximab, Paclitaxel, Pertuzumab, and Trastuzumab unique for treating breast cancer?

This drug combination is unique because it includes Margetuximab, a newer antibody that targets the same HER2 protein as Trastuzumab but is designed to enhance the immune system's response against cancer cells, potentially offering improved effectiveness over existing treatments that combine Trastuzumab and Pertuzumab with taxane-based chemotherapy. ^{1 2 4 9 10}

What is the purpose of this trial?

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)

Research Team

Adrienne Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

References

1. United States 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. [2023]

2. Netherlands 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. [2021]

3. France pubmed.ncbi.nlm.nih.gov

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

4. China 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Gemcitabine With Trastuzumab and Pertuzumab After Prior Pertuzumab-Based Therapy Among Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: A Phase 2 Clinical Trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Margetuximab plus Chemotherapy for Advanced or Metastatic HER2-Positive Breast Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. [2018]

8. England pubmed.ncbi.nlm.nih.gov

First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. [2022]

9. England 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. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Management of patients treated with pertuzumab in the Australian clinical practice setting. [2018]