Pembrolizumab + Chemotherapy for Triple Negative Breast Cancer

Recruiting at 192 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

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

1174 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475) plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy and pembrolizumab vs placebo as adjuvant therapy in participants who have triple negative breast cancer (TNBC). After a screening phase of approximately 28 days, each participant will receive neoadjuvant study treatment (Pembrolizumab + Chemotherapy OR Placebo + Chemotherapy) based on the randomization schedule for approximately 24 weeks (8 cycles). Each participant will then undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant study treatment. After definitive surgery, each participant will receive adjuvant study treatment (Pembrolizumab OR Placebo) for approximately 27 weeks (9 cycles). Following adjuvant study treatment, each participant will be monitored for safety, survival and disease recurrence. The primary study hypothesis is that pembrolizumab is superior to placebo, in combination with chemotherapy, as measured by the rate of Pathological Complete Response (pCR) and/or Event-free Survival (EFS), in participants with locally advanced TNBC.

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.

What data supports the effectiveness of the drug Pembrolizumab combined with chemotherapy for treating triple-negative breast cancer?

A Phase II trial showed that combining pembrolizumab with chemotherapy, including carboplatin, resulted in a 48% overall response rate in patients with metastatic triple-negative breast cancer, with some patients experiencing complete or partial responses lasting over 6 months. Additionally, a network meta-analysis indicated that adding carboplatin or pembrolizumab to treatment regimens improved the rate of complete response in triple-negative breast cancer. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and chemotherapy safe for humans?

The safety of chemotherapy drugs like filgrastim and pegfilgrastim, which are used to prevent low white blood cell counts, has been studied in breast cancer patients. These drugs are generally safe and help reduce the risk of infection during chemotherapy, although some patients may still experience infections. ^{6 7 8 9 10}

What makes the drug Pembrolizumab combined with chemotherapy unique for treating triple-negative breast cancer?

Pembrolizumab combined with chemotherapy is unique for treating triple-negative breast cancer because it enhances the body's immune response against cancer cells and has shown improved outcomes like pathologic complete response and survival rates compared to chemotherapy alone. This combination is particularly effective in patients with high PD-L1 levels, offering a novel approach by integrating immunotherapy with traditional chemotherapy. ^{11 12 13 14 15}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Investigating potential immune mechanisms of trilaciclib administered prior to chemotherapy in patients with metastatic triple-negative breast cancer. [2023]

2. China 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]. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Neo-adjuvant therapy for triple-negative breast cancer: Insights from a network meta-analysis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Association of Immunophenotype With Pathologic Complete Response to Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: A Secondary Analysis of the BrighTNess Phase 3 Randomized Clinical Trial. [2023]

6. Indonesia pubmed.ncbi.nlm.nih.gov

Factors Associated with Absolute Neutrophil Count Dynamics and Docetaxel-Adryamicin-Cyclophosphamide (TAC) Chemotherapy Induced Neutropenia During Extended Filgrastim Administration in Breast Cancer Patients. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Assessing the Optimal Regimen: A Systematic Review and Network Meta-Analysis of the Efficacy and Safety of Long-Acting Granulocyte Colony-Stimulating Factors in Patients with Breast Cancer. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on pegfilgrastim in chemotherapy-induced neutropenia. [2018]

10. England pubmed.ncbi.nlm.nih.gov

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

11. England 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). [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant Pembrolizumab Takes on TNBC. [2020]

13. United States pubmed.ncbi.nlm.nih.gov

Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer: NeoPACT Phase 2 Clinical Trial. [2023]

14. England 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. [2021]

15. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy in Japanese patients with triple-negative breast cancer: Results from KEYNOTE-355. [2023]