Pembrolizumab for Triple-Negative Breast Cancer

Not currently recruiting at 1081 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunotherapy, Biologic therapy

Disqualifiers: Metastatic disease, Active autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 48

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab for individuals with triple-negative breast cancer. Pembrolizumab, an immunotherapy, helps the immune system attack cancer cells and may prevent their growth and spread. Participants will either receive pembrolizumab or undergo observation to assess the treatment's effectiveness. This trial suits those who have undergone surgery and chemotherapy for triple-negative breast cancer but still have residual cancer. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants the opportunity to contribute to the development of a promising treatment.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot receive certain therapies like other immunotherapies or biologic therapies during the trial. It's best to discuss your specific medications with the trial team.

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. Studies have found that combining this treatment with chemotherapy can extend patient survival compared to chemotherapy alone. However, pembrolizumab, like any treatment, can cause side effects. Some patients have experienced immune-related side effects, such as rash, fatigue, or inflammation in various parts of the body.

Pembrolizumab is already approved for treating other types of cancer, indicating a certain level of established safety. While side effects can occur, many patients manage them effectively with medical assistance. Prospective trial participants should discuss potential risks and benefits with their healthcare provider to gain a clearer understanding of what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for triple-negative breast cancer, which often include chemotherapy, Pembrolizumab offers a fresh approach by harnessing the immune system. Pembrolizumab is a type of immunotherapy that works by blocking the PD-1 pathway, a mechanism that cancer cells use to hide from immune attacks. This unique action helps the immune system recognize and destroy cancer cells more effectively. Researchers are excited about Pembrolizumab because it has the potential to provide a more targeted treatment option with possibly fewer side effects than traditional chemotherapy.

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

Research has shown that pembrolizumab, which participants in this trial may receive, may help treat triple-negative breast cancer. In studies, patients who received pembrolizumab with chemotherapy lived longer than those who only had chemotherapy. Specifically, pembrolizumab reduced the risk of cancer progression by 35% compared to a placebo. Other studies found that more patients had no detectable cancer after treatment. These results suggest pembrolizumab could be a promising option for this type of breast cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Lajos Pusztai

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with triple-negative breast cancer who've completed neoadjuvant chemotherapy and surgery, have no metastatic or recurrent disease, and no active hepatitis or infections. They must not be pregnant/nursing, have had certain prior treatments (like anti-HER2 therapies), live vaccines recently, or autoimmune diseases treated in the last 2 years.

Inclusion Criteria

My cancer has not spread to distant parts of my body.

Your platelet count is at least 100,000 per microliter.

You need to order specimen kits at least two weeks before registering the first patient at your site.

Exclusion Criteria

I am not HER2-positive according to specific cancer guidelines.

My cancer is weakly ER/PR positive and I'm not eligible for hormone therapy.

My cancer has not returned in the same place it was treated.

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 42 days for 52 weeks

52 weeks

Visits every 42 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 6 months for 5 years, then annually

Long-term follow-up

Participants are monitored annually for long-term outcomes

5 additional years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview

The study tests Pembrolizumab as an additional treatment after standard therapy for triple-negative breast cancer. It's a phase III trial to see if this immunotherapy can prevent cancer from returning by helping the immune system attack remaining cancer cells.

How Is the Trial Designed?

Group I: Arm II (pembrolizumab) Experimental Treatment 6 Interventions

Patients receive pembrolizumab IV over 30 minutes on days 1 and 22. Cycles repeat every 42 days for 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may undergo radiation therapy within 12 weeks of last breast cancer operation or after treatment. Patients may also undergo collection of blood samples throughout the trial.

Group II: Arm I (observation) Experimental Treatment 6 Interventions

Patients receive no treatment but are monitored at standard clinical intervals during first year after randomization. Patients are examined every 12 weeks for 1 year, every 6 months for 4 years, and then annually for 5 years. Patients may undergo radiation therapy within 12 weeks of last breast cancer operation or after treatment. Patients may also undergo collection of blood samples throughout the trial.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

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 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]

In a phase 3 trial involving 622 patients with metastatic triple-negative breast cancer, pembrolizumab did not significantly improve overall survival compared to standard chemotherapy, with median survival times of 9.9 months for pembrolizumab and 10.8 months for chemotherapy.

Pembrolizumab showed a manageable safety profile, with fewer severe treatment-related adverse events compared to chemotherapy, suggesting it may be safer for some patients despite not demonstrating superior efficacy overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Winer, EP., Lipatov, O., Im, SA., et al.[2021]

Pembrolizumab, when combined with chemotherapy, significantly improves pathological complete response (pCR) and event-free survival (EFS) in patients with high-risk, early-stage triple-negative breast cancer, as shown in the KEYNOTE-522 trial with 123 EFS events in the pembrolizumab group compared to 93 in the control group.

Despite 44% of patients experiencing immune-related adverse reactions, the benefits of pembrolizumab, including a 7.5% absolute improvement in pCR rates, support its use as an effective neoadjuvant and adjuvant treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer. Shah, M., Osgood, CL., Amatya, AK., et al.[2023]

In a phase 3 trial involving 847 patients with untreated metastatic triple-negative breast cancer, the addition of pembrolizumab to chemotherapy significantly improved progression-free survival, especially in patients with a PD-L1 combined positive score (CPS) of 10 or more, with a median survival of 9.7 months compared to 5.6 months for placebo.

The safety profile of pembrolizumab-chemotherapy was comparable to placebo-chemotherapy, with similar rates of grade 3-5 treatment-related adverse events (68% vs. 67%), indicating that the combination therapy is both effective and manageable in terms of safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Cortes, J., Cescon, DW., Rugo, HS., et al.[2021]

In the KEYNOTE-086 study involving 254 patients with metastatic triple-negative breast cancer, several biomarkers such as PD-L1, CD8, stromal tumor-infiltrating lymphocytes (sTILs), tumor mutational burden (TMB), and T-cell-inflamed gene expression profile (TcellinfGEP) were significantly associated with better clinical outcomes when treated with pembrolizumab.

These findings suggest that assessing these biomarkers can help identify which patients are more likely to benefit from pembrolizumab monotherapy, enhancing personalized treatment strategies for metastatic triple-negative breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. Loi, S., Salgado, R., Schmid, P., et al.[2023]

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]

Citations

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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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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 ...

Neoadjuvant pembrolizumab has shown efficacy in improving pathologic complete response (pCR) rates and survival outcomes in triple-negative breast cancer (TNBC ...

4.

keytruda.com

keytruda.com/triple-negative-breast-cancer/clinical-trial-results/advanced-tnbc/

Triple-negative breast cancer (TNBC) - clinical trials

KEYTRUDA + chemotherapy reduced the risk of cancer spreading, growing, or getting worse by 35% compared to placebo + chemotherapy.

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.

sciencedirect.com

sciencedirect.com/science/article/pii/S0960977625004904

Immune-related adverse events among patients with early ...

This study aims to describe patterns of irAEs in a real-world scenario during treatment with pembrolizumab for early-stage TNBC.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02447003

NCT02447003 | Study of Pembrolizumab (MK-3475) ...

This is a two-part study of pembrolizumab monotherapy in participants with metastatic triple-negative breast cancer (mTNBC).