Radiation + Immunotherapy for Breast Cancer

(BreastVAX Trial)

Overseen By Michelle Gelman

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Pregnancy, Autoimmune disease, Active infection, 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: 3

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining pembrolizumab, a type of immunotherapy, with a single dose of radiation is effective and safe for individuals with early-stage or operable breast cancer. Researchers seek to evaluate how well this combination shrinks tumors and how the immune system responds. The trial includes different groups: one group will receive pembrolizumab before radiation, another will receive radiation before pembrolizumab, and a control group will not receive these treatments. Suitable candidates include those newly diagnosed with breast cancer smaller than 5 cm, not recommended for standard chemotherapy, or those with locally recurrent breast cancer expecting surgery. As a Phase 1/Phase 2 trial, this study focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group.

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, it mentions that participants should not have received certain cancer therapies recently and should not have active infections requiring treatment. 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 pembrolizumab, a drug approved by the FDA for other cancers, can cause side effects, including serious immune system reactions. However, when combined with chemotherapy, pembrolizumab has extended the lives of some breast cancer patients.

Studies on hypofractionated radiotherapy, a radiation treatment given in larger doses over a shorter period, indicate it is generally well-tolerated. Most patients experience mild skin reactions, and serious side effects are rare.

This trial tests pembrolizumab with radiation, so the overall safety will depend on their combined effects. Previous research has shown that each treatment is safe individually, but their combination is still under study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining pembrolizumab with radiation for breast cancer because it targets the immune system differently than standard treatments. Pembrolizumab is an immunotherapy drug that boosts the body's immune response specifically against cancer cells, potentially enhancing the effects of radiation. Unlike traditional chemotherapy, which attacks both healthy and cancerous cells, this approach aims to increase precision and reduce side effects. This combination could offer faster results, showing effectiveness within days, compared to the weeks it often takes with conventional treatments.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that pembrolizumab, a type of immunotherapy, can help treat breast cancer. In some studies, nearly a third of patients initially scheduled for a mastectomy opted for less invasive surgery instead. This indicates that pembrolizumab can shrink tumors enough to simplify surgery. In this trial, one group will receive pembrolizumab followed by radiotherapy, while another group will receive radiotherapy followed by pembrolizumab. Hypofractionated radiotherapy, a shorter but more intense radiation treatment, has also been shown to reduce the chance of cancer recurrence and improve survival rates. Together, these treatments might enhance the body's immune response against cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Julia C Tchou, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early-stage breast cancer who can handle radiation therapy and have good overall health. They must not have had recent cancer treatments, no severe psychiatric or substance abuse issues, no active infections or certain viruses like HIV, Hepatitis B/C, and should not be pregnant.

Inclusion Criteria

My blood, kidney, liver, thyroid, and bone marrow are functioning well.

I am fully active or restricted in physically strenuous activity but can do light work.

My breast cancer is in the early stages and I'm not receiving certain types of chemotherapy.

Exclusion Criteria

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial

I have been diagnosed with HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Treatment

Participants receive either pembrolizumab followed by radiotherapy or radiotherapy followed by pembrolizumab

2 weeks

2 visits (in-person)

Surgery

Participants undergo surgery on day 0

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood and tissue sampling

2 years

Regular visits (in-person) for blood and tissue sampling

What Are the Treatments Tested in This Trial?

Interventions

• Blood and tissue sampling
• Hypofractionated radiotherapy
• Pembrolizumab

Trial Overview The study tests if adding a single dose of radiation (hypofractionated radiotherapy) to pembrolizumab (an immune therapy drug) is feasible in treating early breast cancer. It also looks at how the tumor responds clinically and immunologically before and after treatment.

How Is the Trial Designed?

Group I: Arm 4 (Historical Controls) Experimental Treatment 1 Intervention

Arm 4 will not receive any study treatment. Subjects will undergo surgery on day 0 and follow a preoperative (Day 0) and postoperative blood (Day 30) and tissue (Day 0) sampling schedule.

Group II: Arm 2 Active Control 3 Interventions

Arm 2 will receive pembrolizumab on day -14 and radiotherapy on day -7. Subjects in all arms will undergo surgery on day 0 and follow the same postoperative blood sampling and safety schedule.

Group III: Arm 1 Active Control 3 Interventions

Arm 1 will receive radiotherapy on day -14 and pembrolizumab on day -7. Subjects in all arms will undergo surgery on day 0 and follow the same postoperative blood sampling and safety schedule.

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?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

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, 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]

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, 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]

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 (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

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]

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]

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 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]

Citations

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Once-Weekly Ultra-Hypofractionated Radiation Therapy for ... This study reports outcomes of once-weekly adjuvant whole-breast radiotherapy in elderly and/or comorbid patients with breast cancer, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12364632/

Impact on outcomes of ultra hypofractionation or ... Overall, it reduced the risk of recurrence by 16% at 10 years and breast cancer-specific survival by 4% at 15 years. Different groups exhibit ...

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Are Three Weeks of Whole-Breast Radiotherapy as Good ... At 10 years, 71.3% of women in the control group as compared with 69.8% of the women in the hypofractionated-radiation group had a good or excellent cosmetic ...

4. ascopubs.org ascopubs.org/doi/10.1200/GO-24-00277

Phase II Evaluation of Ultra-Hypofractionated ... The study found that ultra-hypofractionated radiation therapy in patients with breast cancer had low rates of acute toxicity and cosmesis changes.

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Hypofractionated breast radiotherapy for 1 week versus 3 ... FAST-Forward results confirm that 26 Gy in five fractions is as effective and safe as an international standard 15-fraction regimen after ...

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Efficacy and safety analysis of hypofractionated and ... In this meta-analysis, we conducted a comparative analysis of the safety and efficacy of hypofractionated and conventional fractionated ...

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Real World Safety of Adjuvant Ultra Hypofractionated ... Ultra-hypofractionated breast radiotherapy (26 Gy in 5 fractions) was well tolerated. · More than half of patients showed no skin toxicity; grade ...

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Hypofractionated whole breast radiotherapy Hypofractionated RT following BCS is safe and effective ... Table 1 summarizes the long-term outcomes of four carefully conducted, randomized trials, involving ...

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A Randomized Trial of Hypofractionated Post-Mastectomy ... The 24-month month incidence of reconstruction complications was 14% (59/422) with hypofractionation vs 11.7% (47/403) with conventional PMRT, ...