Pembrolizumab + Chemotherapy for Breast Cancer

Recruiting at 262 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: CDK4/6 inhibitors

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Cardiac disease, Active infection, CNS metastases, 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

Compensation: Varies

Number of Visits: 3

Duration: Up to 35 cycles

340 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain treatments like systemic steroids or investigational agents, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Pembrolizumab + Chemotherapy for Breast Cancer?

Research shows that liposomal doxorubicin, a component of the treatment, is effective in treating breast cancer and has a better safety profile compared to non-liposomal forms. Additionally, the combination of paclitaxel and doxorubicin in liposomal form has shown promise in controlling breast cancer and lung metastasis in animal models. ^{1 2 3 4 5}

Is the combination of pembrolizumab and chemotherapy safe for breast cancer patients?

The combination of pembrolizumab with paclitaxel or capecitabine has been shown to be safe in a clinical trial for breast cancer, with most patients able to complete treatment without severe side effects. However, both regimens can reduce white blood cell counts, which are important for fighting infections. ^{6 7 8 9 10}

What makes the drug combination of Pembrolizumab, Capecitabine, Liposomal Doxorubicin, and Paclitaxel unique for breast cancer treatment?

This drug combination is unique because it combines Pembrolizumab, an immune therapy that helps the body's immune system fight cancer, with chemotherapy drugs like Capecitabine, Liposomal Doxorubicin, and Paclitaxel, which are designed to kill cancer cells. The use of Liposomal Doxorubicin is particularly notable as it is less harmful to the heart compared to traditional forms, and it may enhance the immune response when used with Pembrolizumab. ^{1 2 5 11 12}

What is the purpose of this trial?

The safety and efficacy of pembrolizumab plus the investigator's choice of chemotherapy will be assessed compared to placebo plus the investigator's choice of chemotherapy in the treatment of chemotherapy-candidate hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) locally recurrent inoperable or metastatic breast cancer. The primary hypotheses are that the combination of pembrolizumab and chemotherapy is superior to placebo and chemotherapy in regards to Progression-Free Survival (PFS) in participants with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥1.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with HR+/HER2- breast cancer that's locally recurrent and inoperable or has spread (metastatic), who haven't had chemotherapy for this condition before, but have progressed after endocrine therapy. They should be candidates for chemotherapy, have a certain level of PD-L1 protein on their tumor cells, good organ function, measurable disease per RECIST 1.1 criteria, and an ECOG performance status of 0 or 1.

Inclusion Criteria

My organs are functioning well, as tested within the last 10 days.

Your disease can be measured using a specific set of guidelines by your doctor.

I am Hepatitis B positive but have been on HBV antiviral therapy for over 4 weeks with an undetectable viral load.

Exclusion Criteria

I have been treated with immunotherapy before.

I have a BRCA mutation and haven't been treated with PARP inhibitors.

I have an active case of tuberculosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab or placebo plus chemotherapy

Up to 35 cycles

Visits every 3-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 76 months

Treatment Details

Interventions

• Capecitabine
• Liposomal Doxorubicin
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests if pembrolizumab combined with the investigator's choice of chemotherapy improves survival without cancer progression compared to placebo plus chemotherapy in patients whose tumors express PD-L1. The effectiveness will be measured by how long patients live without their disease getting worse (PFS) and overall survival (OS).

Participant Groups

Group I: Pembrolizumab + Chemotherapy Experimental Treatment 5 Interventions

Participants receive pembrolizumab 200 mg administered by intravenous infusion (IV) on Day 1 of each 21-day cycle (Q3W) PLUS one of four chemotherapy regimens: 1) paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle (Q4W), 2) nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 Q4W, 3) liposomal doxorubicin 50 mg/m\^2 IV on Day 1 Q4W, OR 4) capecitabine 1000 mg/m\^2 by oral administration (PO) twice a day (BID) on Days 1-14 Q3W for up to 35 administrations.

Group II: Placebo + Chemotherapy Active Control 6 Interventions

Participants receive placebo (normal saline or dextrose) IV on Day 1 Q3W PLUS one of four chemotherapy regimens: 1) paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 Q4W, 2) nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 Q4W, 3) liposomal doxorubicin 50 mg/m\^2 IV on Day 1 Q4W, OR 4) capecitabine 1000 mg/m\^2 PO BID on Days 1-14 Q3W for up to 35 administrations.

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

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast 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 the PELICAN trial involving 210 patients with metastatic breast cancer, pegylated liposomal doxorubicin (PLD) and capecitabine showed similar efficacy, with a median time-to-disease progression of 6.0 months for both treatments.

However, capecitabine was associated with a higher incidence of serious adverse events compared to PLD, suggesting that PLD may have a better safety profile, especially for patients with prior anthracycline exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Harbeck, N., Saupe, S., Jäger, E., et al.[2018]

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]

Stealth liposomal doxorubicin (Caelyx, Doxil) shows promise as a treatment for breast cancer, leveraging its unique liposomal formulation to improve drug delivery and efficacy.

The liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics and reduces toxicity compared to traditional non-liposomal doxorubicin, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer. Ranson, MR., Cheeseman, S., White, S., et al.[2019]

In a phase Ib trial involving women with triple-negative breast cancer, both pembrolizumab combined with weekly paclitaxel and with capecitabine were found to be safe, meeting the safety endpoint with 87% and 100% of patients respectively not experiencing severe toxicities.

The efficacy results showed an objective response rate of 29% for the pembrolizumab/paclitaxel combination and 43% for the pembrolizumab/capecitabine combination, indicating that both regimens are clinically active, particularly in patients with specific biomarkers like PD-L1 scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer. Page, DB., Pucilowska, J., Chun, B., et al.[2023]

Trastuzumab deruxtecan (T-DXd) has shown superior efficacy compared to capecitabine-based chemotherapy and T-DM1 in patients with metastatic HER2-positive breast cancer, based on the latest phase III data from the DESTINY-Breast02 and DESTINY-Breast03 trials.

T-DXd may also be effective as a neoadjuvant treatment for HER2-low breast cancer, suggesting its potential for broader applications in HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-DXd Keeps Shining in Breast Cancer. [2023]

The PELICAN-IPC trial is investigating the safety and efficacy of pembrolizumab, an anti-PD-1 antibody, combined with chemotherapy in patients with HER2-negative inflammatory breast cancer (IBC), which is known for its aggressive nature and poor treatment outcomes.

The primary goal of the trial is to assess the rate of pathologic complete response (pCR) after treatment, while also monitoring safety and tolerability, with additional objectives focusing on long-term survival outcomes and translational research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PELICAN-IPC 2015-016/Oncodistinct-003: A Prospective, Multicenter, Open-Label, Randomized, Non-Comparative, Phase II Study of Pembrolizumab in Combination With Neo Adjuvant EC-Paclitaxel Regimen in HER2-Negative Inflammatory Breast Cancer. Bertucci, A., Bertucci, F., Zemmour, C., et al.[2022]

In a meta-analysis of 15 studies involving cancer patients treated with either nivolumab or pembrolizumab, nivolumab was associated with a higher overall incidence of cardiotoxicity (55.7%) compared to pembrolizumab (27.31%), although this difference was not statistically significant.

However, when looking specifically at myocarditis, pembrolizumab showed a significant increase in cardiotoxicity risk, suggesting that while nivolumab may be more commonly reported for general cardiotoxicity, pembrolizumab poses a greater risk for this specific heart condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. Ndjana Lessomo, FY., Wang, Z., Mukuka, C.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

References

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

A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Combined paclitaxel-doxorubicin liposomal results in positive prognosis with infiltrating lymphocytes in lung metastasis. [2021]

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

A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer. [2023]

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

T-DXd Keeps Shining in Breast Cancer. [2023]

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

PELICAN-IPC 2015-016/Oncodistinct-003: A Prospective, Multicenter, Open-Label, Randomized, Non-Comparative, Phase II Study of Pembrolizumab in Combination With Neo Adjuvant EC-Paclitaxel Regimen in HER2-Negative Inflammatory Breast Cancer. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. [2023]

10. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Pegylated Liposomal Doxorubicin, Docetaxel, and Trastuzumab as Neoadjuvant Treatment for HER2-Positive Breast Cancer Patients: A Phase II and Biomarker Study. [2022]

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

Combined pembrolizumab and pegylated liposomal doxorubicin in platinum resistant ovarian cancer: A phase 2 clinical trial. [2021]