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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-arm, open-label, phase 2 study that will enroll 36 subjects, who have pathologically proven diagnosis of invasive breast cancer, clinical stage tumor 1-3 (cT1-T3), node 0-3 (cN0-N3), metastasis 0 (cM0), hormone receptor positive (HR+) (estrogen-receptor-positive (ER+) and/or progesterone-receptor-positive (PR+) human epidermal growth factor receptor 2 (HER2) negative or hormone receptor-negative (HR-) (estrogen-receptor-negative (ER-) and progesterone-receptor-negative (PR-) human epidermal growth factor receptor 2 (HER2) negative/triple-negative breast cancer.

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.

What data supports the idea that Cemiplimab + Chemotherapy for Breast Cancer is an effective treatment?

The available research shows that combinations of chemotherapy drugs like paclitaxel and doxorubicin have been effective in treating breast cancer. For example, one study reported a high response rate of 95% when using doxorubicin plus paclitaxel in patients with advanced breast cancer. Another study highlighted that combinations of drugs like paclitaxel and anthracyclines (such as doxorubicin) have shown significant effectiveness, with response rates as high as 77.1% in some cases. While these studies do not specifically mention Cemiplimab, they suggest that combining chemotherapy drugs can be very effective in treating breast cancer, which supports the idea that Cemiplimab + Chemotherapy could also be effective. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug combination used in the Cemiplimab + Chemotherapy for Breast Cancer trial?

Research shows that paclitaxel and doxorubicin, both part of the trial's drug combination, have been highly effective in treating advanced breast cancer, achieving high response rates and tumor shrinkage. Additionally, taxane-based regimens, like those including paclitaxel, have shown high complete response rates in breast cancer patients. ^{1 2 3 4 5}

What safety data is available for Cemiplimab and chemotherapy in breast cancer treatment?

The safety data for the chemotherapy agents involved in the Cemiplimab + Chemotherapy trial, particularly nab-paclitaxel (Abraxane), indicates that it has a better safety profile compared to conventional paclitaxel, with reduced toxicities. In various studies, nab-paclitaxel has shown to cause less severe neutropenia and peripheral neuropathy compared to other formulations. Neutropenia was the most common adverse event, with grade 3/4 neutropenia occurring in a significant number of patients, but febrile neutropenia was not observed. Peripheral neuropathy was also noted, but mostly at lower grades. These studies suggest that nab-paclitaxel is a safe and effective option in breast cancer treatment, though specific safety data for Cemiplimab in combination with these agents is not detailed in the provided research. ^{2 6 7 8 9}

Is nab-paclitaxel safe for breast cancer treatment?

Nab-paclitaxel, a form of paclitaxel, has been shown to have a better safety profile compared to conventional paclitaxel, with fewer toxicities. It is generally considered safe for breast cancer treatment, although common side effects include neutropenia (low white blood cell count) and peripheral neuropathy (nerve damage causing tingling or numbness). ^{2 6 7 8 9}

Is the drug combination of Cemiplimab, Cyclophosphamide, Doxorubicin, and Paclitaxel promising for breast cancer?

Yes, the drug combination is promising for breast cancer. Doxorubicin and Cyclophosphamide are part of a well-known treatment that has been effective for breast cancer. Paclitaxel, when added to this combination, has shown to improve survival rates and reduce cancer recurrence. These drugs have been used successfully in various combinations to treat breast cancer, making this new combination a hopeful option. ^{1 10 11 12 13}

How is the drug Cemiplimab combined with chemotherapy unique for treating breast cancer?

The combination of Cemiplimab with chemotherapy drugs like cyclophosphamide, doxorubicin, and paclitaxel is unique because it integrates an immunotherapy agent (Cemiplimab) with established chemotherapy drugs, potentially enhancing the immune system's ability to fight breast cancer while also directly targeting cancer cells with chemotherapy. ^{1 10 11 12 13}

Research Team

Lubna N. Chaudhary

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. [2020]

2. Japan 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. [2018]

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

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

4. France pubmed.ncbi.nlm.nih.gov

[Chemotherapy of metastatic breast cancer]. [2009]

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

Paclitaxel and doxorubicin in metastatic breast cancer. [2015]

6. Japan 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]. [2016]

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

Randomized phase II study of nab-paclitaxel as first-line chemotherapy in patients with HER2-negative metastatic breast cancer. [2022]

8. United States 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. [2015]

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

nab-paclitaxel: a novel formulation of taxane for treatment of breast cancer. [2018]

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

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

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

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. [2018]

12. Switzerland 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. [2018]

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

Paclitaxel: as adjuvant or neoadjuvant therapy in early breast cancer. [2018]