Pembrolizumab + Chemotherapy for Breast Cancer

Not currently recruiting at 7 trial locations

Overseen By Elias Obeid, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Pembrolizumab, combined with chemotherapy, is safe and effective for women with metastatic triple-negative breast cancer. Pembrolizumab may help the immune system fight cancer cells, though it has not yet received approval for breast cancer. Participants will receive either Pembrolizumab with chemotherapy (including drugs like Carboplatin and Gemcitabine) or chemotherapy alone to compare outcomes. Women diagnosed with this type of cancer who have not undergone more than three previous treatments might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like immunosuppressive therapy or have had recent chemotherapy or radiation therapy. It's best to discuss your specific medications with the trial team.

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

Research has shown that combining pembrolizumab with chemotherapy has been studied in patients with advanced triple-negative breast cancer. One study found that this combination lowered the risk of death by 27% compared to chemotherapy alone, but only for patients whose tumors had certain markers. This suggests the treatment could be effective and reasonably safe.

The FDA has already approved pembrolizumab for treating other cancers, such as advanced melanoma and advanced non-small cell lung cancer. This approval indicates that the drug's safety is well-understood for those conditions, which is promising for its use in breast cancer.

Chemotherapy drugs like carboplatin and gemcitabine are well-known and widely used. They have known side effects, but patients generally tolerate them well.

Based on this information and the current stage of the study, pembrolizumab plus chemotherapy appears to be a treatment option with a manageable safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about pembrolizumab plus chemotherapy because it offers a new approach for treating breast cancer. Unlike standard treatments that rely solely on chemotherapy drugs like carboplatin and gemcitabine, pembrolizumab is an immunotherapy. It works by blocking the PD-1 pathway, which helps the immune system recognize and attack cancer cells more effectively. This combination could potentially enhance the effectiveness of chemotherapy and lead to better outcomes for patients.

What evidence suggests that Pembrolizumab combined with chemotherapy could be an effective treatment for metastatic triple negative breast cancer?

In this trial, participants will receive either Pembrolizumab with standard chemotherapy or standard chemotherapy alone. Research has shown that combining Pembrolizumab with chemotherapy might be more effective for treating advanced triple-negative breast cancer than chemotherapy alone. Specifically, a study found that patients who received this combination treatment lived longer overall. For instance, after 60 months, 86.6% of patients in the pembrolizumab-chemotherapy group were still alive. Pembrolizumab enhances the immune system's ability to identify and destroy cancer cells. While it is already approved for treating advanced melanoma and lung cancer, its use in breast cancer remains under investigation. Early results suggest it could benefit patients. ^{1 6 7 8 9}

Who Is on the Research Team?

Elias Obeid, MD

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with metastatic triple negative breast cancer who haven't had certain treatments in the last few weeks and have adequate organ function. They must not be pregnant, agree to use birth control, and provide tissue samples. Exclusions include other active cancers, severe health conditions, or recent participation in another investigational study.

Inclusion Criteria

I am eligible for chemotherapy with carboplatin and gemcitabine.

My cancer can be measured by scans.

My cancer has spread and cannot be removed by surgery.

Exclusion Criteria

I have a weakened immune system or have been on steroids or other immune-weakening drugs in the last 4 weeks.

You live outside the United States.

Patients participating in another trial of an investigational agent within 4 weeks of the first dose of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pembrolizumab in combination with carboplatin and gemcitabine

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Gemcitabine
• Pembrolizumab

Trial Overview The trial tests Pembrolizumab combined with chemotherapy drugs Carboplatin and Gemcitabine for safety and effectiveness against metastatic triple negative breast cancer. Pembrolizumab has been used for melanoma and lung cancer but isn't yet approved for breast cancer treatment.

How Is the Trial Designed?

Group I: Pembrolizumab with Standard Chemotherapy Experimental Treatment 3 Interventions

Pembrolizumab plus standard chemotherapy using carboplatin and gemcitabine.

Group II: Standard Chemotherapy Alone Active Control 2 Interventions

Standard chemotherapy alone using carboplatin and gemcitabine.

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?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

In a phase II study involving 22 patients with BRCA1/2-related metastatic breast cancer, the combination of pembrolizumab and carboplatin showed an overall response rate (ORR) of 43% and a disease control rate (DCR) of 76%, indicating some level of efficacy, particularly in luminal tumors.

Despite the promising results, the study did not meet its primary aim of achieving an ORR of 70%, leading to its termination; however, the safety profile was acceptable with only 22.7% of patients experiencing grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). Cortesi, L., Venturelli, M., Cortesi, G., et al.[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]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, is generally well tolerated, but can lead to rare immune-mediated adverse effects such as pleuropericarditis, as seen in a case involving a 64-year-old female patient.

The patient was effectively treated with colchicine, furosemide, and methylprednisolone, leading to symptom improvement and a decision to discontinue pembrolizumab, after which she remained asymptomatic for six months, highlighting the importance of recognizing and managing potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. Suarez, ZK., Finke, AC., Hospedales, E., 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40233520/

Real-world evidence of the efficacy of neoadjuvant ... Pembrolizumab enabled 32.7 % of patients initially planned for mastectomy to undergo breast-conserving surgery (BCS). Axillary lymph node dissection (ALND) was ...

6. nature.com nature.com/articles/s41591-024-03415-7

Pembrolizumab and chemotherapy in high-risk, early-stage ... In summary, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved the pathological complete response rate in patients ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02447003

NCT02447003 | Study of Pembrolizumab (MK-3475) ... Part 1 of the study will examine the efficacy and safety of pembrolizumab monotherapy as first line or above treatment in participants who have received either ...

8. merck.com merck.com/news/mercks-keytruda-pembrolizumab-plus-chemotherapy-reduced-risk-of-death-by-27-versus-chemotherapy-as-first-line-treatment-for-patients-with-metastatic-triple-negative-breast-cancer-whos/

Merck's KEYTRUDA® (pembrolizumab) Plus ... In this study, KEYTRUDA plus chemotherapy reduced the risk of death by 27% (HR=0.73 [95% CI, 0.55-0.95]; p=0.0093) in patients with mTNBC whose tumors expressed ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK596330/

Clinical Review - Pembrolizumab (Keytruda) - NCBI - NIH The predicted 5-year survival rate is 12% for mTNBC compared to 77% for all TNBC and 89% for all breast cancer.-. The standard approach for mTNBC is treatment ...