Pembrolizumab for Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Hormone therapy

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunodeficiency, Autoimmune disease, Pneumonitis, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 22

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of pembrolizumab, an immunotherapy drug, in treating hormone receptor-positive inflammatory breast cancer that remains localized to the breast. The focus is on patients who did not achieve a complete response to chemotherapy and are undergoing hormone therapy. Pembrolizumab may assist the immune system in targeting and fighting cancer cells. Ideal participants have inflammatory breast cancer with symptoms such as rapid breast changes and redness, without cancer spreading to other body parts. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on daily corticosteroids or certain immunosuppressive therapies, you may not be eligible to participate.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research shows that pembrolizumab, a type of immunotherapy drug, is generally well-tolerated in many cancer treatments. It helps the immune system fight cancer cells. In past studies, patients who took pembrolizumab with chemotherapy lived longer than those who only had chemotherapy. However, some people experienced side effects.

One study found that patients often had side effects, which can sometimes be serious. These include fatigue, nausea, and skin reactions. Some patients might also experience immune-related side effects, such as inflammation in different parts of the body.

Pembrolizumab is already approved by the FDA for other types of cancer, providing extensive safety information. However, individual responses vary, and some people might have more side effects than others. Prospective trial participants should discuss any concerns with the medical team conducting the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it harnesses the immune system to fight breast cancer. Most standard treatments for breast cancer, like chemotherapy, target cancer cells directly. However, pembrolizumab is an immunotherapy that works by blocking a protein called PD-1, which helps the immune system recognize and attack cancer cells more effectively. Researchers are excited about pembrolizumab because it offers a new way to treat breast cancer, potentially leading to better outcomes for patients who may not respond well to traditional therapies.

What evidence suggests that pembrolizumab might be an effective treatment for breast cancer?

Research shows that pembrolizumab can help fight certain types of breast cancer. In this trial, patients will receive pembrolizumab as a standalone treatment. For patients with advanced breast cancer, other studies have shown that combining pembrolizumab with chemotherapy can extend survival compared to chemotherapy alone. Additionally, pembrolizumab has enabled some patients to undergo less invasive surgery for breast cancer. This treatment helps the body's immune system find and attack cancer cells, potentially stopping them from growing and spreading. Although more research is needed specifically for hormone receptor-positive inflammatory breast cancer, these results are promising. ^{1 2 6 7 8}

Who Is on the Research Team?

Bora Lim, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with hormone receptor positive inflammatory breast cancer that hasn't spread, who didn't fully respond to chemotherapy and are on hormone therapy. Eligible participants must have a certain level of neutrophils, not be pregnant or become pregnant, have started radiation or endocrine therapy recently if applicable, and meet specific health criteria like normal organ function tests.

Inclusion Criteria

Is willing and able to provide written informed consent for the trial

Participants of reproductive potential must agree to avoid becoming pregnant or impregnating a partner

My cancer did not fully respond to chemotherapy before surgery.

Exclusion Criteria

Is currently participating in a study of an investigational anti-cancer agent

I have an immune system disorder or am on drugs that weaken my immune system.

I have an autoimmune disease that needed treatment in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously every 21 days for up to 24 months

24 months

Cycles repeat every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Follow-up at 1 and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview

The trial is testing pembrolizumab's effectiveness in these patients. Pembrolizumab is an immunotherapy drug that may boost the immune system's ability to fight cancer by blocking tumor growth. This phase II study will assess how well it works when other treatments haven't led to complete cancer removal.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab) Experimental Treatment 1 Intervention

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In patients with hormone receptor-positive metastatic breast cancer, higher levels of specific immune cells (effector memory CD8+ and CD4+ T cells) before treatment were associated with better responses to the combination therapy of palbociclib, pembrolizumab, and letrozole, compared to those receiving only pembrolizumab and letrozole.

The combination therapy also led to significant changes in myeloid cell composition, including increased mature dendritic cells and decreased classical monocytes, which may enhance the immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. Egelston, C., Guo, W., Yost, S., et al.[2021]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39282906/

Overall Survival with Pembrolizumab in Early-Stage Triple ...

The estimated overall survival at 60 months was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the pembrolizumab-chemotherapy group, as ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2202809

Pembrolizumab plus Chemotherapy in Advanced Triple ...

In this trial, first-line treatment with pembrolizumab–chemotherapy resulted in significantly longer overall survival than chemotherapy alone ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40233520/

Real-world evidence of the efficacy of neoadjuvant ...

Pembrolizumab enabled 32.7 % of patients initially planned for mastectomy to undergo breast-conserving surgery (BCS). Axillary lymph node dissection (ALND) was ...

4.

keytrudahcp.com

keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab)

The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%). In KEYNOTE⁠-⁠671, adverse reactions ...

5.

nature.com

nature.com/articles/s41523-025-00814-y

Association of potential biomarkers with clinical outcomes ...

In the randomized, phase 3 KEYNOTE-119 study, overall survival (OS) was not significantly improved with pembrolizumab 200 mg Q3W versus ...

6.

nature.com

nature.com/articles/s41591-024-03415-7

Pembrolizumab and chemotherapy in high-risk, early-stage ...

In summary, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved the pathological complete response rate in patients ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03036488

NCT03036488 | Study of Pembrolizumab (MK-3475) Plus ...

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475) plus chemotherapy vs placebo plus chemotherapy as neoadjuvant ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2949820124000390

Real-world safety and effectiveness of neoadjuvant ...

Patients experience high rates of toxicity with risk of long-term morbidity and mortality. irAE rates in our real-life cohort were higher than those described ...