Pembrolizumab + Standard Therapy for Breast Cancer

Not currently recruiting at 335 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Pneumonitis, Metastatic cancer, Autoimmune, others

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

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 explores whether adding pembrolizumab (an immunotherapy drug) to standard chemotherapy and hormone therapy, both before and after surgery, can more effectively treat certain types of breast cancer. It targets high-risk early-stage breast cancer that is estrogen receptor-positive (ER+) and lacks an excess of the HER2 protein. The researchers aim to determine if this combination improves outcomes compared to a placebo. Individuals diagnosed with ER+/HER2- breast cancer who have not yet undergone surgery might be suitable candidates for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive therapy or steroids, you may need to stop, as these are part of the exclusion criteria.

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

Research shows that pembrolizumab, a key part of this trial, has been tested with chemotherapy for other types of breast cancer. Safety information from these studies indicates that pembrolizumab might cause immune-related side effects. These side effects can affect different parts of the body and, in some cases, be serious or even life-threatening. However, such severe reactions are uncommon.

Additionally, previous studies have used pembrolizumab with chemotherapy. This combination helped some patients live longer, suggesting a positive balance between benefits and risks. Each person's experience with the treatment can differ, so discussing potential risks and benefits with a healthcare provider is crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer, which typically involve chemotherapy drugs like cyclophosphamide, doxorubicin, epirubicin, and paclitaxel, the new approach includes pembrolizumab, an immunotherapy drug. Pembrolizumab stands out because it works by boosting the body's immune system to better recognize and attack cancer cells, offering a different mechanism of action than traditional chemotherapy. Researchers are particularly excited about pembrolizumab because it has shown promise in other cancers by potentially improving outcomes and reducing recurrence rates, which could represent a significant advancement in breast cancer treatment.

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

Research has shown that combining pembrolizumab with chemotherapy can improve survival rates for breast cancer patients. In this trial, participants in one arm will receive pembrolizumab with chemotherapy. Studies have found that this combination leads to longer survival compared to chemotherapy alone. Specifically, one study reported that 86.6% of patients receiving this combination were still alive after five years, indicating a significant benefit. This finding is particularly important for various types of breast cancer, including more aggressive forms. These results suggest that pembrolizumab may enhance the effectiveness of standard cancer treatments, offering hope for better outcomes in high-risk early-stage breast cancer. ^{5 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

Adults with high-risk early-stage ER+/HER2- breast cancer, confirmed by a pathologist, who have not received prior treatment for it. Participants must have adequate organ function and an ECOG performance status of 0 or 1. Men and women must agree to use contraception during the study and for some time after. Exclusions include those with certain heart diseases, active infections like hepatitis B/C or tuberculosis, HIV, other cancers within the last five years (except specific non-invasive types), previous immunotherapy treatments, severe allergies to study drugs' components.

Inclusion Criteria

I agree to use contraception and not donate sperm for up to 12 months after treatment.

My breast cancer is ER positive, HER2 negative, Grade 3, and of ductal type.

My breast cancer is invasive, not just on the surface, and is a certain size or has spread to nearby lymph nodes.

Exclusion Criteria

I haven't used any experimental drugs or devices within the last 4 weeks, or 12 months if they were for cancer.

I have an active tuberculosis infection.

My breast cancer is estrogen receptor-negative and progesterone receptor-positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant chemotherapy with either pembrolizumab or placebo in combination with paclitaxel, doxorubicin or epirubicin, and cyclophosphamide for 8 cycles

24 weeks

8 cycles (21 days each)

Surgery

Participants undergo surgery for breast cancer after completion of neoadjuvant treatment

Up to 6 weeks post-treatment

Adjuvant Treatment

Participants receive adjuvant therapy with either pembrolizumab or placebo for 9 cycles and variable endocrine therapy for up to 10 years

27 weeks for pembrolizumab/placebo, up to 10 years for endocrine therapy

9 cycles (21 days each)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Endocrine therapy
• Epirubicin
• Paclitaxel
• Pembrolizumab
• Placebo
• Radiation therapy
• Surgery

Trial Overview The trial is testing pembrolizumab's effectiveness compared to a placebo when given alongside pre-surgery chemotherapy and post-surgery endocrine therapy in treating early-stage breast cancer. Success is measured by complete response rate at surgery and event-free survival rates.

How Is the Trial Designed?

Group I: Pembrolizumab+Chemotherapy (KX/KA[E]C) Experimental Treatment 8 Interventions

In the neoadjuvant setting, participants receive pembrolizumab (K) 200 mg via intravenous (IV) infusion once every 3 weeks (Q3W) + paclitaxel (X) 80 mg/m\^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by pembrolizumab 200 mg via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m\^2 or 100 mg/m\^2) via IV infusion either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive pembrolizumab 200 mg via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long.

Group II: Placebo+Chemotherapy (PX/PA[E]C) Placebo Group 7 Interventions

In the neoadjuvant setting, participants receive placebo (P; normal saline or dextrose) via IV infusion Q3W + paclitaxel (X) 80 mg/m\^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by placebo via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m\^2 or 100 mg/m\^2) via IV infusion either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive placebo via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

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

In a study of 152 patients with HER2-positive metastatic breast cancer, the combination of taxanes with trastuzumab and pertuzumab showed a significant progression-free survival (PFS) advantage over vinorelbine in patients with newly diagnosed metastatic disease, indicating a potential benefit for this specific group.

Overall, there was no significant difference in overall survival (OS) between the two treatment groups, suggesting that both taxanes and vinorelbine are viable options when combined with trastuzumab and pertuzumab for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study. Reinhorn, D., Kuchuk, I., Shochat, T., et al.[2021]

The combination therapy of doxorubicin and paclitaxel (AT) showed a superior overall response rate (47%) and longer median time to treatment failure (8.0 months) compared to single-agent therapies, although the difference in survival rates was not significant.

Both doxorubicin and paclitaxel demonstrated equivalent efficacy, with median survivals of 18.9 months for doxorubicin and 22.2 months for paclitaxel, indicating that while combination therapy may enhance response rates, it does not necessarily lead to improved survival or quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). Sledge, GW., Neuberg, D., Bernardo, P., et al.[2022]

Nab-paclitaxel, a novel formulation of paclitaxel, has shown higher response rates and a better safety profile compared to conventional paclitaxel in a Phase III study, leading to its approval for treating breast cancer after prior chemotherapy failure.

Ongoing Phase II studies are investigating nab-paclitaxel's effectiveness as a first-line treatment for metastatic breast cancer and its potential use in other solid tumors, indicating its expanding role in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-paclitaxel: a novel formulation of taxane for treatment of breast cancer. Vishnu, P., Roy, V.[2018]

Paclitaxel, when combined with doxorubicin, has shown a remarkable 95% objective response rate in chemotherapy-naive patients with metastatic breast cancer, indicating its high efficacy in treating this condition.

The treatment regimen demonstrated no signs of cardiac toxicity, allowing for further testing in patients with smaller tumors to potentially increase the rate of complete remission before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future developments for paclitaxel in the treatment of breast cancer. Bonadonna, G.[2015]

The combination of Doxil (40 mg/m2) and vinorelbine (30 mg/m2) was found to be effective in treating metastatic breast cancer in a phase I study involving 30 women, with a recommended schedule for further testing.

This combination therapy demonstrated a favorable toxicity profile, with minimal severe side effects like neutropenia and a low incidence of significant nausea, vomiting, or hair loss, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. Burstein, HJ., Ramirez, MJ., Petros, WP., et al.[2020]

In a phase II clinical trial involving 55 patients with operable breast cancer, preoperative chemotherapy using nanoparticle albumin-bound paclitaxel (nab-PTX) followed by an epirubicin and cyclophosphamide regimen achieved a pathological complete response (pCR) rate of 22.2%, indicating its efficacy in treating this condition.

The study found that HER2-positive patients had a significantly higher pCR rate of 60%, suggesting that HER2 status is an important factor in predicting treatment response, while the overall safety profile of the treatment was considered tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial. Futamura, M., Nagao, Y., Ishihara, K., et al.[2018]

Doxorubicin has historically been the most effective treatment for metastatic breast cancer, especially when combined with other agents like 5-fluorouracil and cyclophosphamide, leading to improved patient outcomes.

New agents such as docetaxel have shown significantly higher response rates than doxorubicin in phase III trials, and importantly, docetaxel does not carry the same risk of cardiotoxicity, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining new agents with anthracyclines in metastatic breast cancer: an overview of recent findings. Aapro, MS.[2018]

Nab-PTX (Abraxane®) was administered to 31 breast cancer patients without any allergic reactions, indicating it is well tolerated, even in those with alcohol intolerance.

Among patients with locally advanced operable breast cancer, higher doses (260 mg/m²) resulted in a better response rate, with 10 out of 13 showing a partial response, suggesting its efficacy in treating advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience of nab-Paclitaxel treatment in 31 patients with breast cancer]. Tauchi, Y., Kashiwagi, S., Ishihara, S., et al.[2015]

The combination of paclitaxel and doxorubicin has significantly improved clinical outcomes for breast cancer patients, particularly in neoadjuvant settings for locally advanced cases.

However, this combination therapy is associated with cardiac toxicity, highlighting the need for careful monitoring and future research to mitigate these risks while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiac tolerance of the combination paclitaxel-anthracyclines in the context of the management of cancer of the breast]. Ferrero, JM., Magné, N., Foa, C., et al.[2015]

Current cytotoxic therapies for metastatic breast cancer show low response rates, and resistance to these treatments is almost always developed, whether initially or over time.

There is a critical need for new therapies that can improve overall survival in patients who have developed resistance to standard treatments like anthracyclines and taxanes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Other options in the treatment of advanced breast cancer. Cobleigh, MA.[2019]

In a study of 47 elderly women with high-risk breast cancer, the combination of Non-Pegylated Liposomal Doxorubicin (NPL-DOX) and Cyclophosphamide followed by weekly Paclitaxel showed a low rate of cardiac toxicity over a median follow-up of 76 months, with only one case of grade 3 congestive heart failure reported.

While there was a gradual decline in left ventricular ejection fraction (LVEF) over time, it remained above 50% and did not lead to any significant clinical symptoms, indicating that the treatment is relatively safe for cardiac health in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study. Coltelli, L., Finale, C., Musettini, G., et al.[2023]

Citations

1. 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 ...

2. 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. 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 ...

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. 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).

6. keytrudahcp.com keytrudahcp.com/safety/adverse-reactions/triple-negative-breast-cancer/

KEYNOTE-355 - Adverse Reactions & Safety Data Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously.

7. merck.com merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

keytruda_pi.pdf Safety data are available for the first 203 patients who received KEYTRUDA and chemotherapy (n=101) or placebo and chemotherapy (n=102). Patients with ...

8. ema.europa.eu ema.europa.eu/en/documents/product-information/keytruda-epar-product-information_en.pdf

Keytruda, INN-pembrolizumab - EMA Safety data of pembrolizumab in the adjuvant melanoma setting in patients ≥ 75 years are ... triple-negative breast cancer and then continue getting KEYTRUDA ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02954874

NCT02954874 | Testing MK-3475 (Pembrolizumab) as ... This randomized phase III trial studies how well pembrolizumab works in treating patients with triple-negative breast cancer.