Boserolimab + Pembrolizumab + Chemotherapy for Breast Cancer

Recruiting at 1 trial location

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Cardiovascular 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

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

Trial Summary

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or steroids, you may need to stop them at least 7 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Boserolimab, Pembrolizumab, and Chemotherapy for Breast Cancer?

Research shows that adding pembrolizumab to chemotherapy improves survival rates in patients with triple-negative breast cancer, and similar combinations have been effective in other cancers like non-small cell lung cancer. This suggests that the combination of pembrolizumab with chemotherapy could be beneficial for breast cancer treatment. ^{1 2 3 4 5}

Is the combination of Boserolimab, Pembrolizumab, and Chemotherapy safe for breast cancer treatment?

The combination of pembrolizumab with paclitaxel or capecitabine has been shown to be safe in a clinical trial for breast cancer, meeting safety criteria without severe toxicities. However, pembrolizumab can cause immune-related side effects, such as inflammation in various organs, which need to be monitored and managed by healthcare providers. ^{3 6 7 8 9}

How is the drug Boserolimab + Pembrolizumab + Chemotherapy unique for breast cancer treatment?

This treatment combines pembrolizumab, an immune-boosting drug, with chemotherapy to potentially enhance the body's ability to fight breast cancer, especially in aggressive forms like inflammatory breast cancer. Pembrolizumab has shown promise in other cancers by targeting the PD-1 pathway, which helps the immune system attack cancer cells more effectively. ^{5 10 11 12 13}

What is the purpose of this trial?

Researchers want to learn if giving boserolimab (MK-5890) with standard treatment (pembrolizumab and chemotherapy) before surgery can help treat triple negative breast cancer (TNBC). The goals of this study are to learn about the safety of boserolimab given with standard treatment before surgery and to learn if people tolerate it and how many people have no signs of cancer in the tissues and lymph nodes removed during surgery.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for individuals with early-stage, high-risk triple-negative breast cancer that hasn't spread. Participants must have a recent tissue diagnosis and controlled HIV or hepatitis if present. They should be relatively active and able to carry out daily activities (ECOG status 0-1).

Inclusion Criteria

I have a new diagnosis of high-risk, early-stage TNBC that hasn't spread.

I provided a tissue sample for my current breast cancer diagnosis less than 29 days ago.

I have HIV and it is well controlled with medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pembrolizumab, boserolimab, paclitaxel, and carboplatin followed by pembrolizumab, doxorubicin hydrochloride or epirubicin hydrochloride, and cyclophosphamide prior to surgery

Up to approximately 9 months

Surgery

Definitive surgery to assess pathological complete response (pCR)

Adjuvant Treatment

Participants receive pembrolizumab with optional additional adjuvant treatment of physician's choice, capecitabine, or olaparib

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 72 months

Treatment Details

Interventions

• Boserolimab
• Epirubicin Hydrochloride, Paclitaxel, Carboplatin, Doxorubicin (hydrochloride), Cyclophosphamide, Capecitabine, Olaparib
• Pembrolizumab

Trial Overview The study tests Boserolimab combined with Pembrolizumab and chemotherapy before surgery in treating triple-negative breast cancer. It aims to assess the safety of this combination therapy, how well patients tolerate it, and its effectiveness in eliminating cancer signs.

Participant Groups

Group I: Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin Experimental Treatment 9 Interventions

Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.

Group II: Pembrolizumab+ Paclitaxel+ Carboplatin Active Control 8 Interventions

Participants will receive pembrolizumab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a case series of 19 patients with previously treated HER2-positive metastatic breast cancer, the combination of pertuzumab, trastuzumab, and taxane therapy resulted in a median progression-free survival of 4.1 months.

The treatment was associated with minimal adverse effects, showing only a slight decrease in left ventricular ejection fraction (-1%) and no occurrences of neutropenic fever, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination pertuzumab, trastuzumab, and taxane for metastatic breast cancer after first progression: a single institution's experience. Dao, BD., Ho, H., Quintal, LN.[2016]

In the KEYNOTE-522 study involving 1174 patients, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rates, with 58.7% achieving pCR compared to 40.0% in the placebo group, regardless of PD-L1 status.

Event-free survival (EFS) was also enhanced, with a 36-month EFS rate of 91.2% for the pembrolizumab group versus 77.2% for the placebo group, indicating that this treatment combination could be a new standard of care for early triple-negative breast cancer in Asian populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Takahashi, M., Cortés, J., Dent, R., et al.[2023]

In a phase Ib trial involving women with triple-negative breast cancer, both pembrolizumab combined with weekly paclitaxel and with capecitabine were found to be safe, meeting the safety endpoint with 87% and 100% of patients respectively not experiencing severe toxicities.

The efficacy results showed an objective response rate of 29% for the pembrolizumab/paclitaxel combination and 43% for the pembrolizumab/capecitabine combination, indicating that both regimens are clinically active, particularly in patients with specific biomarkers like PD-L1 scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer. Page, DB., Pucilowska, J., Chun, B., et al.[2023]

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

In a multicenter retrospective analysis of early triple-negative breast cancer (eTNBC) patients treated with pembrolizumab and chemotherapy, the incidence of immune-related adverse events (irAEs) was found to be 63.9%, with 20% of patients experiencing severe (grade 3 or higher) irAEs.

The study reported a pathological complete response (pCR) rate of 57.1%, with a significant correlation between the occurrence of irAEs and higher pCR rates (72.2% vs. 30.8%), indicating that while irAEs are common, they may be associated with better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer. Marhold, M., Udovica, S., Halstead, A., et al.[2023]

Pembrolizumab is an effective cancer treatment that works by reactivating T cells, but it can lead to various immune-related adverse events, including rare cases of synovitis.

Healthcare providers should be vigilant about the potential for pembrolizumab-induced synovitis and act quickly to treat it to prevent lasting joint damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could knee inflammatory synovitis be induced by pembrolizumab? Mahmoud, F., Wilkinson, JT., Gizinski, A., et al.[2018]

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., et al.[2022]

In a phase II trial involving 50 patients with early triple-negative breast cancer, 66% achieved a pathological complete response (pCR) after treatment with nab-paclitaxel and pembrolizumab, indicating a promising efficacy of this combination therapy.

The treatment was associated with manageable side effects, with fatigue, peripheral sensory neuropathy, and neutropenia being the most common adverse events, suggesting that this regimen could be a viable alternative to platinum-based chemotherapy for patients who cannot tolerate it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041). Fasching, PA., Hein, A., Kolberg, HC., et al.[2023]

Pembrolizumab, a monoclonal antibody that blocks PD-1, effectively enhances antitumor immune responses and has been approved for treating advanced melanoma, renal cell cancer, and non-small cell lung cancer.

In vivo studies using PET imaging showed that pembrolizumab is stable in circulation and primarily accumulates in the liver and spleen, providing valuable insights into its pharmacokinetics and potential for optimizing dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Pharmacokinetics and Biodistribution Studies of 89Zr-Labeled Pembrolizumab. England, CG., Ehlerding, EB., Hernandez, R., et al.[2020]

The PELICAN-IPC trial is investigating the safety and efficacy of pembrolizumab, an anti-PD-1 antibody, combined with chemotherapy in patients with HER2-negative inflammatory breast cancer (IBC), which is known for its aggressive nature and poor treatment outcomes.

The primary goal of the trial is to assess the rate of pathologic complete response (pCR) after treatment, while also monitoring safety and tolerability, with additional objectives focusing on long-term survival outcomes and translational research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PELICAN-IPC 2015-016/Oncodistinct-003: A Prospective, Multicenter, Open-Label, Randomized, Non-Comparative, Phase II Study of Pembrolizumab in Combination With Neo Adjuvant EC-Paclitaxel Regimen in HER2-Negative Inflammatory Breast Cancer. Bertucci, A., Bertucci, F., Zemmour, C., et al.[2022]

References

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

Combination pertuzumab, trastuzumab, and taxane for metastatic breast cancer after first progression: a single institution's experience. [2016]

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

Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. [2023]

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

A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer. [2023]

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

Pembrolizumab plus chemotherapy in Japanese patients with triple-negative breast cancer: Results from KEYNOTE-355. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. [2022]

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

Multicenter phase II study of oral capecitabine (Xeloda(")) in patients with metastatic breast cancer relapsing after treatment with a taxane-containing therapy. [2022]

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

Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer. [2023]

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

Could knee inflammatory synovitis be induced by pembrolizumab? [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-tumor activity of capecitabine and vinorelbine in patients with anthracycline- and taxane-pretreated metastatic breast cancer: findings from the EORTC 10001 randomized phase II trial. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041). [2023]

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

Preclinical Pharmacokinetics and Biodistribution Studies of 89Zr-Labeled Pembrolizumab. [2020]

13. Switzerland pubmed.ncbi.nlm.nih.gov

PELICAN-IPC 2015-016/Oncodistinct-003: A Prospective, Multicenter, Open-Label, Randomized, Non-Comparative, Phase II Study of Pembrolizumab in Combination With Neo Adjuvant EC-Paclitaxel Regimen in HER2-Negative Inflammatory Breast Cancer. [2022]