Cemiplimab + Chemotherapy for Breast Cancer

(CemiHALT Trial)

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Metastatic disease, HER2 positive, 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: Unknown

Duration: 27 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of cemiplimab (an immunotherapy drug) and chemotherapy to evaluate their effectiveness in treating certain types of breast cancer. The focus is on patients with invasive breast cancer that is either hormone receptor-positive or triple-negative, but not HER2 positive. Participants should have a breast cancer diagnosis confirmed by a doctor and may qualify if they have not received prior treatment for this cancer and are eligible for chemotherapy before surgery. The trial aims to determine the treatment's effectiveness and to explore its potential benefits and side effects. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot take systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks before the study or during the study, unless it's a low dose equivalent to ≤ 10mg of prednisone within 7 days prior to study entry.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are on systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to the study, unless it's a low dose. It's best to discuss your specific medications with the study team.

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

Research has shown that the treatments in this study have been used safely in other contexts. For instance, paclitaxel is generally well-tolerated, with mild nerve damage as the main side effect. In some cases, this nerve issue was more serious, but it improved quickly over time.

Cyclophosphamide, another treatment in the study, has previously been used to treat breast cancer. Severe side effects occurred in some patients, but these were rare, and most people found the drug manageable.

Specific information on cemiplimab's safety is not available in the current sources. However, since this study is in an earlier phase, cemiplimab has shown some promise in terms of safety in past research. This is important to consider when evaluating the potential risks and benefits of joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for breast cancer?

Researchers are excited about the combination of cemiplimab with chemotherapy for breast cancer because it represents a novel approach by adding an immunotherapy component. While standard treatments like chemotherapy primarily target rapidly dividing cancer cells, cemiplimab is a type of immunotherapy that helps the immune system recognize and attack cancer cells more effectively. This dual approach aims to enhance the overall effectiveness of treatment, potentially leading to better outcomes. Additionally, cemiplimab's mechanism of action, which blocks a protein called PD-1 on immune cells, is designed to unmask cancer cells, making them more susceptible to immune attacks. This could offer new hope for patients, particularly those who may not respond as well to traditional therapies alone.

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

Research shows that cemiplimab, a drug that aids the immune system, can enhance the body's ability to fight cancer by blocking a protein that prevents immune attacks on cancer cells. In this trial, participants will receive a combination of treatments: cemiplimab, paclitaxel, cyclophosphamide, and doxorubicin. Paclitaxel, commonly used for breast cancer, has proven effective, leading to better response rates and longer periods without cancer progression in patients with advanced breast cancer. Cyclophosphamide boosts the body's response to other cancer treatments. Doxorubicin, a well-known chemotherapy drug, kills cancer cells and is often used for breast cancer. Strong evidence supports the effectiveness of each treatment for different cancer types, and their combination could be a powerful approach for breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Lubna N. Chaudhary

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for women with invasive breast cancer that's either hormone receptor positive and HER2 negative, or triple-negative. They should be candidates for neoadjuvant chemotherapy, have no prior treatments for this cancer or any other malignancy in the past two years (except certain non-melanoma skin cancers), and must not be pregnant or breastfeeding. Participants need to agree to use contraception if of childbearing potential.

Inclusion Criteria

I have cancer in both breasts, both are HER2 negative, and I am considered for chemotherapy before surgery.

I am using two forms of birth control and will continue for 6 months after my last chemo dose.

I have had a CT, bone, PET scan, or MRI as my doctor thought was necessary.

Exclusion Criteria

I haven't taken any experimental drugs or had immunotherapy or chemotherapy for my breast cancer in the last 30 days.

I am a man diagnosed with breast cancer.

I haven't taken strong immune system medications in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemotherapy and cemiplimab

27 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cemiplimab
• Cyclophosphamide
• Doxorubicin
• Paclitaxel

Trial Overview The study tests Cemiplimab alone or with a combination of Paclitaxel, optional Carboplatin, Doxorubicin, and Cyclophosphamide in patients with high-risk or locally advanced breast cancer. It's an open-label phase 2 trial where all participants receive the experimental treatment without a comparison group.

How Is the Trial Designed?

Group I: Drug Treatment Experimental Treatment 5 Interventions

Cemiplimab, Paclitaxel, Carboplatin (not mandatory), Doxorubicin, Cyclophosphamide

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

In two large randomized trials, adding intravenous paclitaxel to standard doxorubicin-cyclophosphamide (AC) therapy significantly improved disease-free survival at 5 years for women with early breast cancer, with one trial also showing improved overall survival.

While paclitaxel demonstrated efficacy in neoadjuvant therapy by increasing response rates and eligibility for breast-conserving surgery, it was associated with notable grade 3-4 adverse events, primarily hematological issues like neutropenia and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel: as adjuvant or neoadjuvant therapy in early breast cancer. Simpson, D., Plosker, GL.[2018]

In a phase II clinical trial involving 55 patients with operable breast cancer, preoperative chemotherapy using nanoparticle albumin-bound paclitaxel (nab-PTX) followed by an epirubicin and cyclophosphamide regimen achieved a pathological complete response (pCR) rate of 22.2%, indicating its efficacy in treating this condition.

The study found that HER2-positive patients had a significantly higher pCR rate of 60%, suggesting that HER2 status is an important factor in predicting treatment response, while the overall safety profile of the treatment was considered tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial. Futamura, M., Nagao, Y., Ishihara, K., et al.[2018]

In a phase II study involving 200 Japanese patients with metastatic breast cancer, weekly nab-paclitaxel showed similar efficacy to docetaxel, with median progression-free survival of 9.8 months for nab-paclitaxel compared to 11.2 months for docetaxel, indicating that both treatments are effective options.

Nab-paclitaxel had a lower incidence of severe neutropenia (35.0%) compared to docetaxel (89.0%), suggesting a potentially safer profile regarding this common side effect, although both treatments had similar overall adverse event rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of nab-paclitaxel as first-line chemotherapy in patients with HER2-negative metastatic breast cancer. Tamura, K., Inoue, K., Masuda, N., et al.[2022]

In a study of 13 HER2-positive breast cancer patients, those treated with nanoparticle albumin-bound paclitaxel (nabPTX) as part of neoadjuvant chemotherapy achieved a significantly higher pathological complete response (pCR) rate of 85.7% compared to 50.0% for those receiving standard paclitaxel.

While nabPTX treatment was associated with a higher incidence of Grade 3/4 neutropenia, it did not lead to any cases of febrile neutropenia, suggesting it may be a safe and effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Neoadjuvant Chemotherapy Containing Nanoparticle Albumin-Bound Paclitaxel (NabPTX) in Operable Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer]. Yoshioka, S., Ota, C., Moriguchi, Y.[2016]

The combination of Doxil (40 mg/m2) and vinorelbine (30 mg/m2) was found to be effective in treating metastatic breast cancer in a phase I study involving 30 women, with a recommended schedule for further testing.

This combination therapy demonstrated a favorable toxicity profile, with minimal severe side effects like neutropenia and a low incidence of significant nausea, vomiting, or hair loss, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. Burstein, HJ., Ramirez, MJ., Petros, WP., et al.[2020]

Combining paclitaxel with doxorubicin has shown impressive remission rates for metastatic breast cancer, with overall rates exceeding 90% and nearly 50% achieving complete remission, especially when administered in a specific sequence.

While other combinations of paclitaxel with drugs like cisplatin and vinorelbine have shown variable results, the doxorubicin/paclitaxel combination remains the most effective and tolerable treatment option currently available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. Hortobagyi, GN., Ibrahim, N.[2018]

In a phase II study involving 66 women with locally advanced breast cancer, the combination of albumin-bound paclitaxel and sequential anthracycline-based therapy resulted in a pathologic complete response (pCR) rate of 29%, with a notably higher pCR of 58% in HER2-positive patients.

The treatment was well tolerated, with manageable side effects, including 16% experiencing grade 2/3 neuropathy and 7% experiencing grade 3/4 febrile neutropenia, suggesting that albumin-bound paclitaxel is a promising option for further evaluation in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II neoadjuvant trial of sequential nanoparticle albumin-bound paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide in locally advanced breast cancer. Robidoux, A., Buzdar, AU., Quinaux, E., et al.[2015]

In a phase II study involving 72 patients with metastatic breast cancer who had previously received anthracycline treatment, the combination of vinorelbine and mitoxantrone showed a 49% objective response rate, indicating significant efficacy in this patient population.

The treatment was associated with manageable side effects, including a 46% incidence of grade 3-4 granulocytopenia and 10% experiencing severe cardiotoxicity, suggesting that with careful dose management, this regimen can be a viable option for patients with prior anthracycline exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line vinorelbine-mitoxantrone combination in metastatic breast cancer patients relapsing after an adjuvant anthracycline regimen: results of a phase II study. Llombart-Cussac, A., Pivot, X., Rhor-Alvarado, A., et al.[2018]

Docetaxel, particularly in combination with doxorubicin and cyclophosphamide (the TAC regimen), has been established as an effective treatment for node-positive breast cancer, demonstrating significant efficacy in both metastatic and adjuvant settings.

While the TAC regimen is associated with higher toxicity compared to traditional treatments, the side effects can be managed effectively with colony-stimulating growth factor support, making it a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel, doxorubicin and cyclophosphamide (the TAC regimen): an effective adjuvant treatment for operable breast cancer. Martin, M.[2016]

Paclitaxel, when combined with doxorubicin, has shown a remarkable 95% objective response rate in chemotherapy-naive patients with metastatic breast cancer, indicating its high efficacy in treating this condition.

The treatment regimen demonstrated no signs of cardiac toxicity, allowing for further testing in patients with smaller tumors to potentially increase the rate of complete remission before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future developments for paclitaxel in the treatment of breast cancer. Bonadonna, G.[2015]

The response to induction chemotherapy is the most important predictor of treatment outcomes in metastatic breast cancer, with anthracyclines and taxanes showing high response rates and long durations of response.

Combination therapies, such as vinorelbine with doxorubicin or epirubicin, have achieved impressive objective response rates, indicating that these combinations can significantly enhance treatment effectiveness for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy of metastatic breast cancer]. Brun, B., Pouillart, P.[2009]

Paclitaxel has shown high effectiveness in treating advanced breast cancer, including cases resistant to anthracyclines, prompting research into its combination with anthracyclines like doxorubicin.

Clinical trials of the paclitaxel/doxorubicin combination have reported promising response rates, although the toxicity profiles vary significantly based on the administration schedule used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and doxorubicin in metastatic breast cancer. Gehl, J., Boesgaard, M., Paaske, T., et al.[2015]

Nab-paclitaxel, a novel formulation of paclitaxel, has shown higher response rates and a better safety profile compared to conventional paclitaxel in a Phase III study, leading to its approval for treating breast cancer after prior chemotherapy failure.

Ongoing Phase II studies are investigating nab-paclitaxel's effectiveness as a first-line treatment for metastatic breast cancer and its potential use in other solid tumors, indicating its expanding role in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-paclitaxel: a novel formulation of taxane for treatment of breast cancer. Vishnu, P., Roy, V.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35121644/

Evaluating the efficacy of a priming dose of cyclophosphamide ... Results: Median PFS was 1.8 months, and the ORR was 21%. Tregs were not significantly decreased after Cy prior to ICI (-3.3%, p=0.19), and increased ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9164196/

Increased intensification and total dose of cyclophosphamide ... Results: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in ...

3. nature.com nature.com/articles/s41598-024-64042-3

Combined oral low-dose cyclophosphamide endocrine ... Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses.

4. nejm.org nejm.org/doi/full/10.1056/NEJM199504063321401

Adjuvant Cyclophosphamide, Methotrexate, and ... After adjuvant chemotherapy with CMF, 47 percent of the premenopausal women were alive at 20 years, as compared with 22 percent of the ...

5. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/bcr2570

Cyclophosphamide- metabolizing enzyme polymorphisms ... These data support the hypothesis that genetic variability in cyclophosphamide metabolism independently impacts outcome from adjuvant chemotherapy for breast ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7882311/

Efficacy and safety of cyclophosphamide in anthracycline- ... Conclusions. AT-based NAC with or without cyclophosphamide showed similar clinical outcomes in patients with operable breast cancer. The addition of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10791571/

Ten-year clinical outcome, toxicity and compliance of dose ... A total of 331 severe adverse events (Grades 3–4) were reported in 228 patients (22.4%), with 108 patients experiencing more than one severe adverse event ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526820924001848

Clinical Breast Cancer PC-H demonstrated overall safety and efficacy, yielding high rates of relapse-free survival among patients with early stage (HER2+) breast cancer.

9. mdpi.com mdpi.com/1718-7729/32/8/441

Efficacy and Safety of Dose-Dense Chemotherapy in ... Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients.

10. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419356364

Long-term outcomes after adjuvant treatment of sequential ... This 10-year analysis of the BCIRG-005 trial confirmed that the efficacy of TAC was not superior to AC → T in women with node-positive early breast cancer.