Pembrolizumab + Chemotherapy for Triple Negative Breast Cancer

No longer recruiting at 247 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids, Live vaccines, others

Disqualifiers: Invasive malignancy, Autoimmune disease, Cardiovascular disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 17

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding pembrolizumab, a type of immunotherapy, to standard chemotherapy is more effective and safer than chemotherapy alone for people with triple-negative breast cancer. The study examines how well the combination shrinks the cancer before surgery and prevents its return afterward. People recently diagnosed with locally advanced triple-negative breast cancer who have not yet received treatment might be suitable candidates. Participants will receive different treatments and be closely monitored for their health and cancer progress. 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 information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive drugs, you may need to stop them before starting the trial.

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

Research has shown that pembrolizumab, when combined with chemotherapy, is usually well-tolerated by patients with triple-negative breast cancer (TNBC). Studies have found that this combination can extend patients' lives compared to chemotherapy alone, indicating that pembrolizumab is generally safe. Real-world data also supports the safety of using pembrolizumab with chemotherapy in TNBC patients, with many handling the treatment well without serious issues. While side effects can occur, these studies reassure that pembrolizumab is a safe and effective option for individuals with this type of breast cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about pembrolizumab combined with chemotherapy for triple-negative breast cancer because it introduces a novel approach by harnessing the power of the immune system. Unlike traditional treatments like chemotherapy alone, pembrolizumab is an immune checkpoint inhibitor that enhances the body's immune response to attack cancer cells. This combination has the potential to improve outcomes by targeting and destroying cancer cells more effectively, offering new hope for patients with this aggressive cancer type.

What evidence suggests that pembrolizumab plus chemotherapy could be an effective treatment for triple negative breast cancer?

Research has shown that pembrolizumab, one of the treatments in this trial, when combined with chemotherapy, yields promising results for treating triple-negative breast cancer (TNBC). Studies have found it increases the likelihood of the cancer disappearing completely and improves survival rates. Specifically, one study demonstrated that using pembrolizumab with chemotherapy reduced the risk of the cancer spreading or worsening by 35% compared to a placebo with chemotherapy, which is another arm in this trial. Additionally, after five years, 86.6% of participants who received pembrolizumab with chemotherapy were still alive. These findings suggest that pembrolizumab could be an effective treatment option for TNBC. ^{1 2 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with untreated, locally advanced triple negative breast cancer (TNBC) without metastasis. Participants must have good performance status, adequate organ function, and agree to use contraception. Excluded are those with hypersensitivities, HIV, active infections or significant heart disease; recent participants in other trials; pregnant or breastfeeding women; and those with certain medical histories.

Inclusion Criteria

My triple-negative breast cancer has not spread beyond my breast and nearby lymph nodes.

I have been recently diagnosed with a specific type of aggressive breast cancer.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I am currently being treated for an infection.

I have an active tuberculosis infection.

Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 4 weeks of the first dose of treatment in this current study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Neoadjuvant Treatment

Participants receive Pembrolizumab plus Chemotherapy or Placebo plus Chemotherapy for approximately 24 weeks (8 cycles) before surgery

24 weeks

8 cycles (in-person)

Surgery

Participants undergo definitive surgery 3-6 weeks after the last cycle of neoadjuvant treatment

3-6 weeks

Adjuvant Treatment

Participants receive Pembrolizumab or Placebo for approximately 27 weeks (9 cycles) post-surgery

27 weeks

9 cycles (in-person)

Follow-up

Participants are monitored for safety, survival, and disease recurrence

Up to 8 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cyclophosphamide
• Epirubicin
• Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim
• Pembrolizumab

Trial Overview The study tests if pembrolizumab combined with chemotherapy is more effective than placebo plus chemotherapy before surgery (neoadjuvant therapy), and if pembrolizumab alone is better than placebo after surgery (adjuvant therapy) in improving survival rates and reducing cancer recurrence in TNBC patients.

How Is the Trial Designed?

Group I: Pembrolizumab + Chemotherapy Experimental Treatment 7 Interventions

Participants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.

Group II: Placebo + Chemotherapy Active Control 7 Interventions

Participants receive placebo (normal saline solution) Q3W + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by placebo + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of placebo Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

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

Published Research Related to This Trial

Pegfilgrastim (Neulasta) is effective in preventing chemotherapy-induced neutropenia and can be given as a single subcutaneous dose of 6 mg per chemotherapy cycle, which is comparable in safety and efficacy to daily injections of filgrastim (Neupogen).

Clinical trials and post-registrational studies are ongoing to explore additional uses of pegfilgrastim, including its application in dose-dense chemotherapy regimens and in the mobilization and engraftment of autologous stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegfilgrastim: a granulocyte colony-stimulating factor with sustained duration of action. Lyman, GH.[2019]

In a phase II trial involving patients with metastatic triple-negative breast cancer, administering trilaciclib before chemotherapy (gemcitabine plus carboplatin) improved overall survival and enhanced T-cell activation, particularly in patients with higher immune-related gene expression.

The combination of trilaciclib and chemotherapy resulted in fewer total T cells and CD8+ T cells, but improved T-cell effector function, indicating that trilaciclib may effectively modulate immune responses in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating potential immune mechanisms of trilaciclib administered prior to chemotherapy in patients with metastatic triple-negative breast cancer. Tan, AR., O'Shaughnessy, J., Cao, S., 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]

In the phase III KEYNOTE-522 trial, pembrolizumab combined with chemotherapy showed increased effectiveness as a neoadjuvant treatment for triple-negative breast cancer, leading to a higher rate of pathologic complete response compared to chemotherapy alone.

This benefit was observed regardless of the PD-L1 expression levels in patients, suggesting that pembrolizumab may be a broadly effective option for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Pembrolizumab Takes on TNBC. [2020]

Vinorelbine-based regimens show moderate efficacy in treating metastatic triple negative breast cancer (mTNBC) in patients previously treated with anthracyclines and taxanes, with an objective response rate of 20.8% and a median overall survival of 15.5 months based on a study of 48 patients.

The combination of vinorelbine with platinum (NP) demonstrated significantly better outcomes compared to vinorelbine with capecitabine (NX), with a higher objective response rate (33.8% vs. 7.7%) and improved progression-free survival (5.3 months vs. 3.0 months), suggesting NP may be a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and toxicity of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes]. Du, F., Yuan, P., Luo, Y., et al.[2018]

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]

Regimens for triple-negative breast cancer (TNBC) that include platinum salts (Pl), pembrolizumab, or bevacizumab significantly improve the rate of pathologic complete response (pCR), indicating their effectiveness in treatment.

However, regimens containing Pl are associated with a higher risk of severe side effects like febrile neutropenia and thrombocytopenia, highlighting the need to balance efficacy with safety in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neo-adjuvant therapy for triple-negative breast cancer: Insights from a network meta-analysis. Miyashita, H., Satoi, S., Cruz, C., et al.[2021]

Citations

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

Pembrolizumab plus Chemotherapy in Advanced Triple ... Pembrolizumab monotherapy has shown durable antitumor activity in advanced triple-negative breast cancer, particularly as first-line therapy, ...

2. 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 ...

3. 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 ...

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. 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).

7. 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.