Pembrolizumab for Breast Cancer

Overseen By Clinton Yam

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active CNS metastases, Autoimmune, 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: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, a type of immunotherapy, to evaluate its effectiveness in treating certain advanced breast cancers. It targets individuals with stage IV inflammatory breast cancer or triple-negative breast cancer that has spread or recurred after treatment. Pembrolizumab helps the immune system attack cancer cells and stop their growth. Participants should have already shown some response or stabilization with previous chemotherapy. This trial may suit those dealing with these specific breast cancers and who have experienced stable disease or a positive response to prior treatment. As a Phase 2 trial, this research measures pembrolizumab's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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 systemic steroid therapy or any form of immunosuppressive therapy, 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 is generally well-tolerated by patients with triple-negative breast cancer. Previous studies found that it effectively targets tumors and is safe to use. The safety profile of pembrolizumab aligns with existing knowledge, and recent studies have identified no new safety concerns. This suggests pembrolizumab is a relatively safe option for those considering trial participation. However, like any treatment, side effects may occur, so discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Pembrolizumab is unique because it leverages the body's immune system to fight breast cancer by blocking a protein called PD-1, which helps cancer cells hide from immune attacks. Unlike traditional chemotherapy that directly kills rapidly dividing cells, pembrolizumab empowers the immune system to recognize and destroy cancer cells more effectively. Researchers are excited about pembrolizumab because it offers a targeted approach, potentially leading to fewer side effects and improved outcomes for patients with breast cancer. Additionally, its administration schedule, starting with every 21 days and then extending to every 42 days, may offer more convenience compared to some standard therapies.

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

Research has shown that combining pembrolizumab with chemotherapy extends survival in patients with advanced triple-negative breast cancer compared to chemotherapy alone. One study found that about 87% of patients treated with both pembrolizumab and chemotherapy were still alive after 60 months. This indicates that pembrolizumab can enhance the immune system's ability to attack cancer cells. Participants in this trial will receive pembrolizumab, a type of immunotherapy that helps the immune system fight cancer and may also slow or stop the cancer from growing and spreading. ^{6 7 8 9 10}

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 stage IV or recurrent inflammatory breast cancer or triple-negative breast cancer who have responded to or remained stable after prior chemotherapy. Participants must be able to consent, have good performance status (0-1 ECOG), use effective birth control, and have adequate organ function. Exclusions include HIV, severe psychiatric/substance abuse issues, recent live vaccines, ongoing anti-cancer treatments, certain autoimmune diseases, active infections requiring systemic therapy.

Inclusion Criteria

My breast cancer is HER2 normal, and may or may not be inflammatory or triple negative.

Has negative serum or urine pregnancy test for participants of childbearing potential

My cancer is HER2 negative based on specific tests.

Exclusion Criteria

Has a known history of human immunodeficiency virus (HIV)

I have an immune system disorder or am on medication that weakens my immune system.

I still have side effects from previous cancer treatments, except for mild neuropathy, hair loss, or general discomfort.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200mg IV every 21 days for 8 cycles, then 400mg IV every 42 days for up to 24 months

Up to 24 months

Every 21 days for 8 cycles, then every 42 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

1 visit at 1 month, 1 visit at 3 months post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial is testing pembrolizumab's effectiveness in treating advanced or returning inflammatory/triple-negative breast cancer that has responded to previous chemo. Pembrolizumab is an immunotherapy drug designed to boost the immune system's ability to fight cancer by blocking a specific pathway known as PD-1/PD-L1.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab) Experimental Treatment 2 Interventions

Patients receive pembrolizumab 200mg IV over approximately 30 minutes on day 1. Cycles repeat every 21 days for 8 cycles and then pembrolizumab 400mg IV every 42 days for total 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 (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]

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, 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]

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]

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]

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 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]

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]

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, 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

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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 ...

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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. 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 ...

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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 ...

5. 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 ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601808

Pembrolizumab (Keytruda) - NCBI Bookshelf - NIH The predicted 5-year survival is 12% for metastatic TNBC compared to 77% for all TNBC and 89% for all breast cancer. The standard approach for metastatic TNBC ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910549

Pembrolizumab for Early Triple-Negative Breast Cancer Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative ...

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

Pembrolizumab and chemotherapy in high-risk, early-stage ... Potential safety risks have been reported in studies investigating cyclin-dependent kinase 4/6 inhibitor plus immune checkpoint inhibitor ...

9. merck.com merck.com/news/pivotal-phase-3-data-for-keytruda-pembrolizumab-in-high-risk-early-stage-triple-negative-breast-cancer-tnbc-published-in-the-new-england-journal-of-medicine/

Pivotal Phase 3 Data for KEYTRUDA® (pembrolizumab) in ... The safety profile of the KEYTRUDA regimen was consistent with the known profiles of each regimen, and no new safety concerns were identified.

10. aacrjournals.org aacrjournals.org/clincancerres/article/24/12/2804/80775/Safety-and-Antitumor-Activity-of-Pembrolizumab-in

Safety and Antitumor Activity of Pembrolizumab in Patients ... These data support further investigation of pembrolizumab alone or in combination with other therapies in the treatment of breast cancer and identification of ...