Combination Therapy for Inflammatory Breast Cancer

Overseen By Vicente Velaro, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticancer therapy, Immunosuppressants

Disqualifiers: Liver disease, Autoimmune 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: Up to 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—atezolizumab, cobimetinib, and eribulin—to evaluate their effectiveness in treating inflammatory breast cancer that has metastasized. The goal is to determine if these drugs work better together to halt cancer growth and spread. Atezolizumab (Tecentriq) aids the immune system in attacking cancer, cobimetinib (Cotellic) inhibits enzymes that promote cancer growth, and eribulin (Halaven) is a chemotherapy drug targeting cancer cells. Individuals with inflammatory breast cancer that has recurred or spread despite standard treatments might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial requires stopping any approved anticancer therapy at least 2 weeks before starting the study treatment. However, certain medications like endocrine therapy and palliative radiotherapy are allowed. The protocol does not specify other medications, so it's best to discuss with the trial team.

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

Research is investigating the safety and effectiveness of a combination of three drugs—atezolizumab, cobimetinib, and eribulin—for treating metastatic inflammatory breast cancer. Previous studies have found that patients generally tolerate these drugs well when used together.

Some studies suggest that the combination of atezolizumab and cobimetinib results in manageable side effects like tiredness and diarrhea. Eribulin, already approved for breast cancer treatment, has typical chemotherapy side effects, such as low white blood cell counts and fatigue.

Another part of the study examines atezolizumab combined with eribulin. This combination also appears promising in terms of safety, though eribulin's known side effects are being closely monitored.

Overall, while side effects exist, as with many cancer treatments, these drug combinations are under study to ensure patient safety. The ongoing phase II trial aims to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for inflammatory breast cancer because they bring a fresh approach to tackling this aggressive condition. Unlike traditional chemotherapy, which targets fast-growing cells, atezolizumab is an immunotherapy that helps the body's immune system recognize and attack cancer cells. Cobimetinib, a MEK inhibitor, works by interfering with specific proteins needed for cancer cell growth, offering a different mechanism of action compared to standard treatments. Additionally, eribulin, a microtubule inhibitor, disrupts the cancer cell division process. This combination aims to provide a multi-faceted attack on cancer cells, potentially leading to more effective outcomes than conventional treatments alone.

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

Studies have shown that a combination of three drugs—atezolizumab, cobimetinib, and eribulin—can be promising for treating metastatic inflammatory breast cancer. In this trial, participants in Cohort I will receive this combination. Atezolizumab, an immunotherapy drug, helps the immune system attack cancer cells. Cobimetinib blocks proteins that aid cancer cell growth. Eribulin, a chemotherapy drug, stops cancer cells from dividing and spreading. Together, these drugs may work better than when used alone. Early research suggests that this combination can potentially improve treatment results for patients. Meanwhile, participants in Cohort II will receive a combination of atezolizumab and eribulin, which researchers are also investigating for its effectiveness in treating this condition. ^{1 2 3 5 6}

Who Is on the Research Team?

Vicente Valero, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with inflammatory breast cancer that has spread (metastatic) and didn't respond to standard treatments. Participants must have measurable disease, be able to provide a biopsy, agree to use contraception, and meet certain health criteria like heart function and blood counts. They shouldn't have had major surgery recently or used some other cancer therapies.

Inclusion Criteria

Your blood needs to have certain levels of different types of cells and chemicals.

Signed informed consent form (ICF) and comply with the requirements of the study protocol

My breast cancer has returned or spread after standard treatment.

Exclusion Criteria

I have a history of lung problems.

I have not had any recent infections requiring antibiotics.

I am not excluded from taking Cobimetinib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive atezolizumab, cobimetinib, and eribulin in cycles, with specific regimens for Cohort I and Cohort II

Up to 6 months

Every 2-3 weeks depending on cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months initially, then every 6 months for 2 years

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Cobimetinib
• Eribulin

Trial Overview

The study tests combining atezolizumab (an immune system booster), cobimetinib (a cell growth blocker), and eribulin (chemotherapy) in treating metastatic inflammatory breast cancer. It's a phase II trial aiming to see if this combo is more effective than current treatments.

How Is the Trial Designed?

Group I: Cohort II (atezolizumab, eribulin) Experimental Treatment 4 Interventions

Patients receive atezolizumab IV over about 30-60 minutes every 3 weeks for cycles 1-6 and every 4 weeks for subsequent cycles, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-6. Cycles 1-6 repeat every 21 days and subsequent cycles with atezolizumab repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Cohort I (atezolizumab, cobimetinib, eribulin) Experimental Treatment 5 Interventions

Patients receive atezolizumab IV over about 30-60 minutes every 2 weeks, cobimetinib PO daily for 3 weeks on, 1 week off for 4 weeks of the safety lead-in course. Patients then receive atezolizumab IV over about 30-60 minutes every 2 weeks, cobimetinib PO daily for 3 weeks on, 1 week off, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-4. Cycles 1-4 repeat every 21 days and subsequent cycles with atezolizumab and cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

In a study of 250 patients with advanced breast cancer, eribulin treatment resulted in a median overall survival of 11.8 months and a median progression-free survival of 4.6 months, indicating its efficacy in this patient population.

The study found that patients who responded well to their last microtubule-inhibiting therapy had significantly longer overall survival when treated with eribulin, suggesting that previous treatment response can help predict the effectiveness of eribulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Results and Analysis of Eribulin Efficacy according to Previous Microtubules-Inhibitors Sensitivity in the French Prospective Expanded Access Program for Heavily Pre-treated Metastatic Breast Cancer. Sabatier, R., Diéras, V., Pivot, X., et al.[2022]

In a phase II study involving 52 patients with locally recurrent or metastatic HER2+ breast cancer, the combination of eribulin and trastuzumab resulted in a high overall response rate (ORR) of 71.2%, indicating significant efficacy as a first-line treatment.

The treatment demonstrated a median progression-free survival (PFS) of 11.6 months and an acceptable safety profile, with the most common severe side effects being neutropenia and peripheral neuropathy, suggesting it is a viable option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2, multicenter, single-arm study of eribulin mesylate with trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer. Wilks, S., Puhalla, S., O'Shaughnessy, J., et al.[2022]

In a phase 1b study involving 103 patients with advanced BRAFV600 wild-type melanoma who had progressed on anti-PD-1 therapy, the combination of cobimetinib and atezolizumab showed an objective response rate of 14.6% and a disease control rate of 38.8%.

The treatment was associated with significant adverse events, including diarrhea (72.8%), dermatitis acneiform (55.3%), and nausea (50.5%), highlighting the need for careful monitoring of side effects despite the limited efficacy observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy. Sandhu, S., Atkinson, V., Cao, MG., et al.[2023]

Atezolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, can cause rare but serious immune-related adverse events (irAEs) such as acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP).

In a case study of a patient receiving atezolizumab, the development of AKI and ITP occurred one week after treatment initiation, but with appropriate management including IVIG and steroids, the patient's condition improved and was discharged for routine follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. Yılmaz, A., Mirili, C., Bilici, M., et al.[2022]

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03202316

Atezolizumab, Cobimetinib, and Eribulin in Treating ...

This phase II trial studies how well atezolizumab, cobimetinib, and eribulin work in treating patients with inflammatory breast cancer that has spread to other ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12182567/

A phase Ib/II trial of atezolizumab with cobimetinib or ...

This phase Ib/II study examined the clinical activity and safety of the novel combination of atezolizumab with molecularly targeted therapy.

3.

mdanderson.org

mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2016-0890.html

A phase II study of triple combination of atezolizumab+ ...

This phase II trial studies how well atezolizumab, cobimetinib, and eribulin work in treating patients with inflammatory breast cancer that has spread to other ...

4.

theibcnetwork.org

theibcnetwork.org/ace-metastatic-ibc/

ACE for metastatic IBC

MEK inhibitors also increase the amount of PD-L1, so by combining Atezolizumab and Cobimetinib together, these drugs work better together. Eribulin is a common ...

5.

researchgate.net

researchgate.net/publication/380301207_Abstract_PO5-06-02_Phase_II_Trial_of_Combination_of_Atezolizumab_Cobimetinib_and_Eribulin_ACE_or_Atezolizumab_and_Eribulin_AE_in_patients_with_metastatic_inflammatory_breast_cancer_IBC_Clinical_data_o

Phase II Trial of Combination of Atezolizumab, Cobimetinib ...

The study closed early due to lack of efficacy in cohort 2 and the changing landscape of metastatic breast cancer therapies. In cohort 1, ...

6.

sigma.larvol.com

sigma.larvol.com/product.php?e1=1390&tab=newstrac&page=36

Tecentriq (atezolizumab) News

Conclusions Overall, genomic subgroups showed results similar to the BEP. While limited by small numbers and lack of long-term data for P+CE, IMbrella A ...