Pembrolizumab for Triple Negative Breast Cancer

(Pembro/IORT Trial)

Recruiting at 2 trial locations

Overseen By Eileen P. Connolly

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Eileen Connolly

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Metastatic disease, Active infection, Autoimmune, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how pembrolizumab, a type of cancer treatment, affects early-stage triple negative breast cancer. Researchers aim to observe changes in immune cells within the tumor and surrounding areas after treatment. Participants will receive the drug before surgery to remove the tumor. The trial seeks women newly diagnosed with early-stage triple negative breast cancer, with a single tumor no larger than 3 cm, and no prior cancer treatments in the last six months. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you may need to stop these before starting the trial.

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

Previous studies have used pembrolizumab in patients with early-stage triple-negative breast cancer (TNBC) and found it generally safe. However, some patients experience side effects due to an overly strong immune response. These side effects can include fatigue, rash, or thyroid problems, but they are often manageable with proper care.

Research shows that intraoperative radiation therapy (IORT) usually results in fewer complications after radiation compared to other methods. It is also known for better cosmetic outcomes, often leaving less noticeable changes to the breast's appearance.

While this specific trial is in an early phase, with safety still being closely monitored, existing data from other uses of pembrolizumab and IORT suggests that both treatments are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for triple negative breast cancer?

Researchers are excited about pembrolizumab for triple negative breast cancer because it works by boosting the immune system to attack cancer cells, a different approach compared to traditional chemotherapy. Pembrolizumab is an immune checkpoint inhibitor that targets the PD-1 pathway, helping the body's immune cells recognize and destroy cancer cells. Another unique feature is its combination with intraoperative radiation therapy (IORT), which delivers targeted radiation directly to the tumor site during surgery, potentially reducing the risk of cancer returning. This combination of immunotherapy with precise radiation could offer significant benefits over existing treatments by enhancing effectiveness while minimizing damage to healthy tissues.

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

Research has shown that pembrolizumab, when combined with chemotherapy, helps patients with triple-negative breast cancer (TNBC) live longer. In earlier studies, patients who received pembrolizumab lived for a median of 23 months, longer than those who only had chemotherapy. It also increased the number of patients whose tumors completely disappeared after treatment. Pembrolizumab enhances the immune system's ability to find and attack cancer cells more effectively. In this trial, participants will receive pembrolizumab before undergoing intraoperative radiation therapy (IORT). Due to its positive results, pembrolizumab is now a standard option for high-risk, early-stage TNBC. ^{2 3 4 6 7}

Who Is on the Research Team?

Eileen Connolly, MD

Principal Investigator

Assistant Professor Of Radiation Oncology

Are You a Good Fit for This Trial?

This trial is for women over 21 with early-stage triple negative breast cancer (TNBC) that's ≤3cm and hasn't spread. They must have good organ function, no prior cancer treatments in the last 6 months, not be pregnant or breastfeeding, and agree to use contraception. Excluded are those with larger tumors, active infections or autoimmune diseases requiring recent treatment, certain other cancers within 5 years, psychiatric/substance issues affecting participation, previous immunotherapy or live vaccines recently.

Inclusion Criteria

I am willing to use birth control during and for 4 months after the study.

Be willing and able to provide written informed consent/assent for the trial

I am 21 years old or older.

Exclusion Criteria

My cancer has spread to other parts of my body.

I have had a stem cell transplant from a donor.

You currently have active Hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two doses of MK-3475 (Pembrolizumab) prior to lumpectomy and intraoperative radiation therapy (IORT)

3 months

1-2 visits for Pembrolizumab administration, 1 visit for IORT

Follow-up

Participants are monitored for changes in tumor-infiltrating lymphocytes (TILs) and other immune markers after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intraoperative radiation therapy (IORT)
• Pembrolizumab

Trial Overview The study tests Pembrolizumab's effects on TNBC before surgery by measuring changes in tumor-infiltrating lymphocytes. Participants receive two doses of Pembrolizumab followed by a lumpectomy where Intraoperative radiation therapy (IORT) is also applied. The goal is to see how the drug alters the tumor environment and immune response.

How Is the Trial Designed?

Group I: Single Arm open label Experimental Treatment 2 Interventions

Participants receive 'Merck 3475 Pembrolizumab' by vein one to two times before Intraoperative radiation therapy (IORT). The Intrabeam® Photon Radiosurgery System is a miniature electron beam-driven X-ray source which provides a point source of low energy X-rays (50 kV maximum) at the tip of a 3.2 mm diameter tube. The radiation source can be inserted into the area of interest immediately after excision of the tumor and switched on for 20-35 minutes to provide intraoperative radiotherapy accurately targeted to the tissues that are at the highest risk of local recurrence. The dosimetric characteristics and early clinical applications of this device have been well studied and this is the device which was utilized in the international TARGIT trial.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Eileen Connolly

Lead Sponsor

Trials

1

Recruited

20+

Merck Sharp & Dohme LLC

Industry 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 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 the KEYNOTE-522 study involving 1174 patients, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rates, with 58.7% achieving pCR compared to 40.0% in the placebo group, regardless of PD-L1 status.

Event-free survival (EFS) was also enhanced, with a 36-month EFS rate of 91.2% for the pembrolizumab group versus 77.2% for the placebo group, indicating that this treatment combination could be a new standard of care for early triple-negative breast cancer in Asian populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Takahashi, M., Cortés, J., Dent, R., 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 KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

In a phase 3 trial involving 847 patients with untreated metastatic triple-negative breast cancer, the addition of pembrolizumab to chemotherapy significantly improved progression-free survival, especially in patients with a PD-L1 combined positive score (CPS) of 10 or more, with a median survival of 9.7 months compared to 5.6 months for placebo.

The safety profile of pembrolizumab-chemotherapy was comparable to placebo-chemotherapy, with similar rates of grade 3-5 treatment-related adverse events (68% vs. 67%), indicating that the combination therapy is both effective and manageable in terms of safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Cortes, J., Cescon, DW., Rugo, HS., et al.[2021]

In the KEYNOTE-086 study involving 254 patients with metastatic triple-negative breast cancer, several biomarkers such as PD-L1, CD8, stromal tumor-infiltrating lymphocytes (sTILs), tumor mutational burden (TMB), and T-cell-inflamed gene expression profile (TcellinfGEP) were significantly associated with better clinical outcomes when treated with pembrolizumab.

These findings suggest that assessing these biomarkers can help identify which patients are more likely to benefit from pembrolizumab monotherapy, enhancing personalized treatment strategies for metastatic triple-negative breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. Loi, S., Salgado, R., Schmid, P., et al.[2023]

Pembrolizumab, when combined with chemotherapy, significantly improves pathological complete response (pCR) and event-free survival (EFS) in patients with high-risk, early-stage triple-negative breast cancer, as shown in the KEYNOTE-522 trial with 123 EFS events in the pembrolizumab group compared to 93 in the control group.

Despite 44% of patients experiencing immune-related adverse reactions, the benefits of pembrolizumab, including a 7.5% absolute improvement in pCR rates, support its use as an effective neoadjuvant and adjuvant treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer. Shah, M., Osgood, CL., Amatya, AK., et al.[2023]

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]

In a multicenter retrospective analysis of early triple-negative breast cancer (eTNBC) patients treated with pembrolizumab and chemotherapy, the incidence of immune-related adverse events (irAEs) was found to be 63.9%, with 20% of patients experiencing severe (grade 3 or higher) irAEs.

The study reported a pathological complete response (pCR) rate of 57.1%, with a significant correlation between the occurrence of irAEs and higher pCR rates (72.2% vs. 30.8%), indicating that while irAEs are common, they may be associated with better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer. Marhold, M., Udovica, S., Halstead, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11493767/

Comparative long-term oncological outcomes ... At a median follow-up of 64.6 months, IORT demonstrated 11 locoregional recurrences (LRR), 1 metastasis, and 1 death, compared to 4 LRR, 5 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2452109423000623

Long-Term Results of Intraoperative Radiation Therapy for ... The 5-year, 10-year, and 15-year overall survival rates were 98.0%, 94.7%, and 88.0%, respectively. Based on univariate analysis, a tumor size of ≤1 cm (pT1a or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9518779/

Triple-negative breast cancer and radiation therapy - PMC Non-basal TNBC had a great benefit from PMRT, reducing recurrence from 64% to 22% (p = 0.03). Conversely, for basal TNBC, the adoption of PMRT had no impact at ...

4. spandidos-publications.com spandidos-publications.com/10.3892/ol.2025.15092

Long‑term follow‑up outcomes of intraoperative ... IORT offers comparable safety, improved cosmesis and greater cost‐effectiveness than PORT, supporting its integration into clinical practice for eligible ...

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.e12530

Intraoperative radiation therapy versus partial breast irradiation ... Conclusions: These results indicate that IORT and PBI confer similar rates of five-year mortality and distant metastatic disease among patients with breast ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10849931/

Outcomes and complications of intraoperative radiotherapy ... IORT is considered to have lower post‐radiation complications and better cosmetic outcomes in breast cancer patients.

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1155/2024/6207762

Outcomes From Real‐World Data on Intraoperative ... Purpose: This study is aimed at investigating the 10-year outcomes of intraoperative radiotherapy (IORT) in Mexican women with early breast ...