Pembrolizumab + Radiation for Breast Cancer

Overseen By Cindi Martin

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Stephen Shiao

Must not be taking: Immunosuppressants, Corticosteroids, Live vaccines, others

Disqualifiers: HER2-positive, Inflammatory breast cancer, Metastatic disease, 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

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating breast cancer by combining pembrolizumab (KEYTRUDA) with radiation, both administered before standard treatments like surgery and chemotherapy. The goal is to determine if this combination is safe and effective in shrinking tumors. The trial seeks participants with certain types of breast cancer treatable with surgery, specifically those with a tumor at least 2 cm in size who plan to undergo breast-conserving therapy. 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 combination 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, you cannot use chronic immunosuppressants or systemic corticosteroids, and you should not have had certain cancer treatments or live vaccines recently. It's best to discuss your specific medications with the study team.

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

Research has shown that using pembrolizumab with radiation therapy is generally safe for breast cancer patients. Studies have found that this combination does not increase the risk of serious side effects, and many patients tolerate this treatment well. For instance, one study found that using pembrolizumab with radiation did not cause more severe reactions than expected, indicating that the treatment is manageable for most people. However, individual experiences can differ, so participants should discuss any concerns with their healthcare team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about the combination of pembrolizumab with a radiation therapy (RT) boost for breast cancer because it offers a novel approach to treatment. Unlike standard therapies like surgery, chemotherapy, or conventional radiation, pembrolizumab is an immunotherapy drug that works by unleashing the body's immune system to attack cancer cells. The addition of a "tumor boost" with targeted radiation aims to enhance the effectiveness of pembrolizumab by directly hitting the tumor with more focused energy. This combination has the potential to not only improve outcomes by shrinking tumors more effectively but also to potentially reduce side effects compared to more aggressive treatments.

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

Research has shown that adding pembrolizumab to treatment plans can enhance the immune system's ability to fight breast cancer. One study found that combining pembrolizumab with chemotherapy improved outcomes for patients with high-risk, early-stage breast cancer. Another study demonstrated that using pembrolizumab with radiation therapy is generally well-tolerated by patients. In this trial, participants will receive pembrolizumab with an RT Boost, a combination that has shown promise in enhancing the effectiveness of cancer treatments. While more information is still needed, these findings suggest that pembrolizumab, when used with radiation, might help the body more effectively destroy cancer cells. ^{6 7 8 9 10}

Who Is on the Research Team?

Stephen Shiao, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with invasive breast cancer, specifically high-risk ER-positive/HER2-negative or triple-negative types without distant metastases. Participants must have a tumor ≥2 cm, be willing to undergo biopsies and adhere to the study schedule. It excludes those with certain cosmetic breast augmentations, other active cancers within 3 years, inflammatory breast cancer, contraindications to radiation therapy or breast-conserving therapy, known HIV/Hepatitis B/C infections, uncontrolled medical disorders or active autoimmune diseases.

Inclusion Criteria

My cancer has been tested for ER, PR, and HER2.

My cancer may or may not have spread to the lymph nodes.

I am fully active or can carry out light work.

Exclusion Criteria

My breast cancer is HER2-positive based on specific test results.

I have an immune system disorder or am on long-term steroids.

I have another cancer that is getting worse or was treated in the last 3 years.

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 pembrolizumab three weeks apart, with radiation therapy (tumor boost) administered at the time of the second dose.

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of tumor-infiltrating lymphocytes and adverse events.

8 weeks

Long-term follow-up

Participants are monitored for disease-free survival and immune-related adverse events.

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• RT Boost

Trial Overview The trial tests pembrolizumab (an immunotherapy drug) combined with a 'tumor boost' of radiation before standard treatments like surgery or chemotherapy. Patients will receive two doses of pembrolizumab three weeks apart; during the second dose they'll also get radiation. Surgery or chemotherapy starts about six weeks after the first dose.

How Is the Trial Designed?

Group I: Pembrolizumab with RT Boost Experimental Treatment 2 Interventions

Study drug plus "tumor boost" before standard of care treatment

Who Is Running the Clinical Trial?

Stephen Shiao

Lead Sponsor

Trials

2

Recruited

100+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a study of 98 patients with advanced non-small-cell lung cancer (NSCLC), those who had previously received radiotherapy experienced significantly longer progression-free survival (4.4 months) and overall survival (10.7 months) when treated with pembrolizumab compared to those without prior radiotherapy.

The safety profile was acceptable, with similar rates of severe pulmonary toxicity between patients who had and had not received thoracic radiotherapy, suggesting that combining radiotherapy with pembrolizumab may be a beneficial treatment strategy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Shaverdian, N., Lisberg, AE., Bornazyan, K., et al.[2022]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a study of 68 patients with advanced solid tumors, the combination of stereotactic body radiotherapy (SBRT) followed by pembrolizumab showed a high one-year treated metastasis control rate of 89.5%, indicating effective tumor response regardless of whether the tumors received complete or partial radiation coverage.

The study found that treated metastasis control (TMC) was significantly associated with improved overall survival, and SBRT altered tumor gene expression by increasing immune-related genes while decreasing those related to cell cycle and DNA repair, suggesting a mechanism for enhanced immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. Luke, JJ., Onderdonk, BE., Bhave, SR., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

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, an immunotherapy targeting PD-1, showed limited effectiveness in a patient with metastatic renal cell carcinoma, highlighting that only 20-40% of patients benefit from such treatments due to individual tumor biology and immune checkpoint diversity.

The patient's rapid disease progression during treatment may be linked to a lack of tumor-infiltrating lymphocytes (TILs) and the specific radiation dose and schedule used, which could affect the tumor microenvironment and the potential synergy with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. Alexander, GS., Palmer, JD., Tuluc, M., et al.[2022]

Radiation therapy not only helps eliminate cancer cells but also modifies the tumor microenvironment, potentially enhancing the body's immune response against tumors.

Combining radiation with immune checkpoint inhibitors has shown promise in early clinical trials for breast cancer, suggesting a synergistic effect that could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Combining Radiation and Immunotherapy in Breast Cancer. Nguyen, AT., Shiao, SL., McArthur, HL.[2021]

Combining anti-HER2 monoclonal antibodies like trastuzumab and pertuzumab with radiation therapy appears to be safe, showing no significant increase in toxicity based on the reviewed literature.

However, caution is advised when combining radiation with tyrosine kinase inhibitors (like lapatinib and tucatinib) and certain antibody-drug conjugates, as the safety of these combinations is not well established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. Debbi, K., Grellier, N., Loganadane, G., et al.[2023]

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 8 patients with hormone receptor-positive metastatic breast cancer, combining pembrolizumab with palliative radiation therapy did not result in any objective responses, leading to the study's closure.

The median progression-free survival was only 1.4 months and overall survival was 2.9 months, indicating limited efficacy of this treatment combination in heavily pre-treated patients, although the treatment was generally safe with only one significant adverse event reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. Barroso-Sousa, R., Krop, IE., Trippa, L., et al.[2021]

In a pooled analysis of 148 patients with metastatic non-small-cell lung cancer, adding radiotherapy to pembrolizumab significantly improved the best out-of-field response rate (41.7% vs 19.7%) and best disease control rate (65.3% vs 43.4%), indicating enhanced efficacy of the combination treatment.

Patients receiving the combination therapy also experienced longer median progression-free survival (9.0 months vs 4.4 months) and overall survival (19.2 months vs 8.7 months) compared to those receiving pembrolizumab alone, with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Theelen, WSME., Chen, D., Verma, V., et al.[2021]

Citations

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Pembrolizumab and chemotherapy in high-risk, early-stage ... Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple- ...

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7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40778461/

Real-world Safety of Concurrent Pembrolizumab and ... Conclusion: Adjuvant radiotherapy can be safely administered concurrently with pembrolizumab in TNBC patients without increasing radiation- ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2452109423002129

Tolerance of Concurrent Adjuvant Radiation Therapy and ... This study aimed to evaluate the tolerance profile of concurrent pembrolizumab with adjuvant RT in patients with locally advanced TNBC.

9. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P5-11-21/752879/Abstract-P5-11-21-Pembrolizumab-impact-on-surgery

Abstract P5-11-21: Pembrolizumab impact on surgery and ... In this study, we aimed to investigate perioperative and radiotherapy (RT)-related toxicities when incorporating pembrolizumab into standard NAC regimens for ...

10. 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).