What side effects are associated with this type of intervention?

Pembrolizumab, an immune checkpoint inhibitor targeting PD-1, is associated with side effects such as fatigue, rash, pruritus, diarrhea, and severe immune-mediated adverse events like pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Common side effects of chemotherapy for breast cancer include nausea, vomiting, hair loss, fatigue, increased risk of infection, and neuropathy. Targeted therapies, such as HER2 inhibitors, can cause diarrhea, liver problems, and heart issues. Hormonal therapies may lead to hot flashes, mood swings, and an increased risk of blood clots.

What prior FDA approvals exist?

Pembrolizumab, an immune checkpoint inhibitor targeting PD-1, has been approved by the FDA for the treatment of certain types of breast cancer, particularly for patients with PD-L1-positive tumors. Another similar drug is atezolizumab, which targets PD-L1 and has been approved for use in combination with nab-paclitaxel for the treatment of PD-L1-positive, triple-negative breast cancer. These approvals highlight the role of immune checkpoint inhibitors in managing breast cancer by enhancing the body's immune response against tumor cells.

What other types of research exist?

Promising alternatives to Pembrolizumab for breast cancer patients include Atezolizumab (targets PD-L1), Nivolumab (targets PD-1), and Cemiplimab (targets PD-1). Additionally, novel therapies such as Relatlimab (targets LAG-3) in combination with Nivolumab, and emerging treatments like CAR-T cell therapy and bispecific antibodies, are showing potential in clinical trials.

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PD-1 Inhibitor

Pembrolizumab + SRS for Brain Metastases from Breast Cancer

Phase 1 & 2

Recruiting

Led By Silvia Formenti, M.D.

Research Sponsored by Weill Medical College of Cornell University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

A diagnostic contrast enhanced MRI demonstrating at least 2 and no more than 10 measurable lesions in the brain, (≥5mm in size), performed within two weeks prior to treatment

Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Must not have

Active connective tissue disorders, such as lupus or scleroderma requiring flare therapy

Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new way to treat breast cancer that has spread to the brain. Patients will receive a drug called pembrolizumab, which will be given before they undergo a type of radiation treatment called stereotactic radiosurgery.

Who is the study for?

This trial is for adults over 18 with metastatic breast cancer and at least two untreated brain metastases visible on MRI. Participants must have good performance status, adequate organ function, and agree to use contraception. Exclusions include recent radiation therapy or immunosuppressive treatment, active infections, other cancers within the past 3 years, severe allergies to pembrolizumab components, certain viral infections like Hepatitis B/C or HIV.

What is being tested?

The study tests pembrolizumab given intravenously every three weeks in combination with stereotactic radiosurgery (SRS) targeting one brain lesion. The goal is to assess the effectiveness of this combined approach in controlling brain metastases from breast cancer.

What are the potential side effects?

Pembrolizumab may cause immune-related side effects such as inflammation of organs including lungs (pneumonitis), liver problems, skin reactions, hormonal gland issues (like thyroid dysfunction), infusion reactions; fatigue and appetite changes are also possible.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My MRI shows 2-10 brain lesions, each at least 5mm, identified within the last two weeks.

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I am fully active or can carry out light work.

Select...

My neurological function is normal or slightly impaired.

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I have breast cancer that has spread to my brain with at least 2 tumors larger than 5mm.

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I am older than 18 years.

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The largest area affected by my cancer is smaller than 4cm.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have an active connective tissue disorder like lupus or scleroderma needing treatment for flares.

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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I have had lung inflammation that needed steroids or have it now.

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I am currently being treated for an infection.

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I have had surgery to remove all detected brain tumors.

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I have a history of Hepatitis B or active Hepatitis C.

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I have an active tuberculosis infection.

Select...

My cancer has spread near my optic nerve.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Correlation of abscopal responses with the radiation dose received

Overall survival - assessed from the start of study drug until death in non-irradiation metastases in the rest of the body by routine imaging.

Tumor response for non-irradiated brain lesions at 8 weeks according to RECIST1.1

Secondary study objectives

Number of participants with abscopal response will be assessed.

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Pembrolizumab and SRSExperimental Treatment1 Intervention

Pembrolizumab infusion will be given on Day 4 (+/-1) after SRS treatment at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for breast cancer include chemotherapy, hormone therapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cancer cells, while hormone therapy blocks hormones like estrogen that fuel certain types of breast cancer. Targeted therapies, such as HER2 inhibitors, specifically target and block the function of proteins that promote cancer cell growth. Immunotherapy, including immune checkpoint inhibitors like pembrolizumab, enhances the body's immune response against cancer cells by blocking the PD-1 pathway, which cancer cells use to evade immune detection. These treatments are crucial as they offer multiple avenues to attack cancer cells, improve survival rates, and provide personalized treatment options based on the specific characteristics of the tumor.

Expanding Therapeutic Options for Older Adults: Case-Based Updates in Breast and Lung Cancer.