Pembrolizumab for Triple-Negative Breast Cancer

Recruiting at 841 trial locations

Overseen By Michelle M. Loch

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Pembrolizumab

Must not be taking: Chronic steroids, Immunosuppressives

Disqualifiers: Metastatic cancer, Active liver disease, 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: Unknown

1295 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether pembrolizumab, a type of immunotherapy, can more effectively prevent the return of early-stage triple-negative breast cancer than simply observing the patient after surgery. Pembrolizumab helps the immune system attack cancer cells and may stop them from growing and spreading. The trial includes individuals who have completed chemotherapy with pembrolizumab and have no remaining invasive cancer after surgery. Those who had certain types of breast cancer and completed chemotherapy before surgery might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop using any investigational anti-cancer agents at the time of registration. If you are on chronic systemic steroids or other immunosuppressive medications, you may not be eligible to participate. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pembrolizumab is generally safe for patients with triple-negative breast cancer. When combined with chemotherapy, it can extend patients' lives. Real-world studies indicate that most patients tolerate this treatment well without serious issues. Common side effects include fatigue, nausea, and skin rash, but these are usually manageable. Since pembrolizumab is already approved for other uses, strong evidence supports its safety in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it harnesses the power of the immune system to fight triple-negative breast cancer, a notoriously tough-to-treat type. Unlike standard treatments like chemotherapy, which attack cancer cells directly, pembrolizumab works by blocking the PD-1 pathway. This pathway can inhibit the immune response, so blocking it helps the immune system recognize and destroy cancer cells. Researchers are excited about pembrolizumab because it offers a new way to potentially improve survival rates and quality of life for patients with this aggressive cancer type.

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

This trial will compare pembrolizumab with observation for patients with triple-negative breast cancer (TNBC). Research has shown that using pembrolizumab with chemotherapy can greatly improve outcomes for TNBC patients. Studies have found that adding pembrolizumab to chemotherapy helps patients live longer and increases the likelihood of no cancer being found in tissue samples after treatment. Specifically, one study discovered that this combination lowers the risk of the cancer worsening or spreading by 35% compared to chemotherapy alone. This suggests that pembrolizumab enhances the immune system's ability to attack cancer cells, potentially improving treatment success for TNBC patients. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early-stage triple-negative breast cancer who had no invasive disease after preoperative chemo and pembrolizumab. They must have completed at least 6 cycles of this treatment, be HIV-positive on effective therapy if applicable, not pregnant or nursing, and without severe active liver disease or a history of certain heart conditions.

Inclusion Criteria

Your total bilirubin level is not more than 1.5 times the upper limit of normal.

Your levels of AST and ALT in your blood should not be more than three times the normal limit.

My breast cancer is mostly not driven by estrogen or progesterone and is not HER2 positive.

Exclusion Criteria

I have never had a severe allergic reaction to pembrolizumab or similar medications.

My cancer has not come back after initial treatment and surgery.

I do not have any active liver diseases like hepatitis or autoimmune disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy in combination with pembrolizumab before surgery

Varies

Definitive Surgery

Participants undergo definitive breast surgery after achieving pathologic complete response

1 day

Adjuvant Treatment or Observation

Participants are randomized to receive either pembrolizumab intravenously or undergo observation

Up to 27 weeks

Follow-up

Participants are monitored for recurrence-free survival, overall survival, and adverse events

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Biopsy
• Biospecimen Collection
• Patient Observation
• Pembrolizumab
• Quality-of-Life Assessment
• Questionnaire Administration

Trial Overview The study compares the effects of continuing pembrolizumab to just observation in patients who've had a complete response to initial treatment. It aims to see if further immunotherapy reduces the risk of cancer returning compared to monitoring without additional drug intervention.

How Is the Trial Designed?

Group I: Arm II (observation) Experimental Treatment 5 Interventions

Patients undergo observation on study. Patients also undergo tumor biopsy on study, and collection of blood on study and during follow-up.

Group II: Arm I (pembrolizumab) Active Control 5 Interventions

Patients receive pembrolizumab IV on study. Patients also undergo tumor biopsy on study, and collection of blood on study and during follow-up.

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?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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 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]

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]

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-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 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]

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]

Citations

1. 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 ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2202809

Pembrolizumab plus Chemotherapy in Advanced Triple ... The addition of pembrolizumab to chemotherapy resulted in significantly longer overall survival than chemotherapy alone.

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

Overall Survival with Pembrolizumab in Early-Stage Triple ... Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in a significant improvement, as compared with ...

4. 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 ...

5. 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.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2949820124000390

Real-world safety and effectiveness of neoadjuvant ... Original article. Real-world safety and effectiveness of neoadjuvant chemotherapy combination with pembrolizumab in triple-negative breast cancer.

7. 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).

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39468438/

Efficacy and Safety of Pembrolizumab Monotherapy or ... This meta-analysis compares the data from numerous relevant studies in order to evaluate the safety and efficacy of pembrolizumab monotherapy or combination ...