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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well atezolizumab, cobimetinib, and eribulin work in treating patients with inflammatory breast cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as eribulin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving atezolizumab, cobimetinib, and eribulin may work better in treating patients with inflammatory breast cancer.

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.

What data supports the effectiveness of the drug combination therapy for inflammatory breast cancer?

Research shows that eribulin, one of the drugs in the combination, is effective in managing advanced breast cancer and may improve survival by affecting the immune system. Additionally, cobimetinib and atezolizumab together have shown promise in treating advanced solid tumors by enhancing the immune response against cancer. ^{1 2 3 4 5}

Is the combination therapy for inflammatory breast cancer safe?

The combination of cobimetinib and atezolizumab has been studied for safety in patients with various solid tumors, showing that while it can be effective, it may cause side effects like immune-related issues such as rash, thyroid problems, and rare kidney issues. Atezolizumab alone has been associated with immune-related side effects, including liver inflammation, lung inflammation, and low platelet counts, but these are not very common. ^{5 6 7 8 9}

How is the drug combination of Atezolizumab, Cobimetinib, and Eribulin unique for treating inflammatory breast cancer?

This drug combination is unique because it combines Atezolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with Eribulin, which affects the structure of cancer cells, and Cobimetinib, which targets specific cancer cell pathways. This multi-faceted approach is different from standard treatments, which often focus on a single mechanism. ^{1 3 4 10 11}

Research Team

Vicente Valero, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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, 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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

High absolute lymphocyte counts are associated with longer overall survival in patients with metastatic breast cancer treated with eribulin-but not with treatment of physician's choice-in the EMBRACE study. [2021]

2. Australia pubmed.ncbi.nlm.nih.gov

Incorporation of eribulin in the systemic treatment of metastatic breast cancer patients in Australia. [2022]

3. Korea (South) 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. [2022]

4. United States 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of cobimetinib plus atezolizumab in patients with solid tumors: a phase II, open-label, multicenter, multicohort study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. [2022]

7. England 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. [2020]

8. England 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

Eribulin plus trastuzumab in pretreated HER2-positive advanced breast cancer patients: safety and efficacy. An Italian experience. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

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