Pembrolizumab + SRS for Brain Metastases from Breast Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Weill Medical College of Cornell University
Must not be taking: Steroids, Immunosuppressants, Live vaccines
Disqualifiers: Autoimmune, Immunodeficiency, Active infection, others
No Placebo Group
Breakthrough Therapy
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?Patients with metastatic breast cancer with at least 2 brain metastases will receive pembrolizumab every 3 weeks. Patients will undergo stereotactic radiosurgery (SRS) to one of the brain lesions. 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.
Will I have to stop taking my current medications?
The trial requires a two-week washout period (time without taking certain medications) from your last systemic treatment before starting the study. However, you can continue using hormonal therapy or anti-Her2 neu therapy if your brain metastases are progressing during these treatments.
What data supports the effectiveness of the drug pembrolizumab for treating brain metastases from breast cancer?
Research shows that pembrolizumab, a drug that helps the immune system fight cancer, has been effective in treating brain metastases from various cancers, with 42.1% of patients experiencing benefits like tumor shrinkage or stabilization. This suggests it might also help some patients with brain metastases from breast cancer.
12345Is the combination of Pembrolizumab and SRS safe for treating brain metastases?
Pembrolizumab, used alone or with radiation therapy like SRS, has shown an acceptable safety profile in treating brain metastases from conditions like melanoma and non-small cell lung cancer, with patients generally not experiencing serious side effects.
13678What makes the drug pembrolizumab unique for treating brain metastases from breast cancer?
Pembrolizumab is unique because it is an immunotherapy drug that works by blocking a protein called PD-1, which helps the immune system attack cancer cells, including those in the brain. This approach is novel for brain metastases, as traditional treatments often do not focus on enhancing the immune response.
1291011Eligibility Criteria
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.Inclusion Criteria
My MRI shows 2-10 brain lesions, each at least 5mm, identified within the last two weeks.
I have had SRS before, but the areas we're looking to treat now haven't been treated with SRS.
I had a partial tumor removal, and any remaining tumor is smaller than 4cm. I can continue hormone or anti-HER2 therapy if my brain cancer worsens.
+11 more
Exclusion Criteria
I have an active connective tissue disorder like lupus or scleroderma needing treatment for flares.
I have not received a live vaccine within the last 30 days.
I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Radiation
Participants undergo stereotactic radiosurgery (SRS) to one of the brain lesions
1 week
1 visit (in-person)
Treatment
Pembrolizumab infusion given every 3 weeks until disease progression or unacceptable toxicity
Variable (until progression or toxicity)
Every 3 weeks (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
3 years
Routine imaging every 3 months
Participant Groups
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.
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.
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brooklyn Methodist Hospital - NewYork PresbyterianNew York, NY
Weill Cornell MedicineNew York, NY
New York Presbyterian Hospital - QueensNew York, NY
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Who Is Running the Clinical Trial?
Weill Medical College of Cornell UniversityLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. [2021]We did a phase 2 trial of pembrolizumab in patients with non-small-cell lung cancer (NSCLC) or melanoma with untreated brain metastases to determine the activity of PD-1 blockade in the CNS. Interim results were previously published, and we now report an updated analysis of the full NSCLC cohort.
Pembrolizumab in brain metastases of diverse histologies: phase 2 trial results. [2023]Brain metastases (BMs) are an emerging challenge in oncology due to increasing incidence and limited treatments. Here, we present results of a single-arm, open-label, phase 2 trial evaluating intracranial efficacy of pembrolizumab, a programmed cell death protein 1 inhibitor, in 9 patients with untreated BMs (cohort A) and 48 patients with recurrent and progressive BMs (cohort B) across different histologies. The primary endpoint was the proportion of patients achieving intracranial benefit, defined by complete response, partial response or stable disease. The primary endpoint was met with an intracranial benefit rate of 42.1% (90% confidence interval (CI): 31-54%). The median overall survival, a secondary endpoint, was 8.0 months (90% CI: 5.5-8.7 months) across both cohorts, 6.5 months (90% CI: 4.5-18.7 months) for cohort A and 8.1 months (90% CI: 5.3-9.6 months) for cohort B. Seven patients (12.3%), encompassing breast, melanoma and sarcoma histologies, had overall survival greater than 2 years. Thirty patients (52%; 90% CI: 41-64%) had one or more grade-3 or higher adverse events that were at least possibly treatment related. Two patients had grade-4 adverse events (cerebral edema) that were deemed at least possibly treatment related. These results suggest that programmed cell death protein 1 blockade may benefit a select group of patients with BMs, and support further studies to identify biomarkers and mechanisms of resistance. ClinicalTrials.gov identifier: NCT02886585.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Outcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1-Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042. [2022]We retrospectively evaluated outcomes in patients with programmed death-ligand 1 (PD-L1)-positive non-small-cell lung cancer (NSCLC) to determine whether baseline (i.e., at study enrollment) brain metastases were associated with the efficacy of pembrolizumab versus chemotherapy.
Upfront pembrolizumab as an effective treatment start in patients with PD-L1 ≥ 50% non-oncogene addicted non-small cell lung cancer and asymptomatic brain metastases: an exploratory analysis. [2021]The efficacy of immune checkpoint inhibitors in patients with brain metastases (BMs) from non-oncogene addicted non-small cell lung cancer (NSCLC) is under investigation. Here, we sought to determine the optimal management of NSCLCs with PD-L1 ≥ 50% and asymptomatic BMs who were treated with first-line pembrolizumab.
Pembrolizumab for non-small cell lung cancer with central nervous system metastases: A two-case report. [2023]Non-small cell lung cancer (NSCLC) accounts for up to 85% of all lung cancers. Central nervous system metastases are a common complication of NSCLC and confer a poor prognosis and a dismal survival rate. Treatment is limited, has poor outcomes, and affects patient quality of life. Pembrolizumab is an anti-PD-1 antibody that has shown good results for the management of NSCLC. However, its penetration of the central nervous system has not been well studied, and patients with untreated brain metastases are excluded from most clinical trials. Herein, we report two cases of NSCLC with brain metastases in patients successfully treated with pembrolizumab, and discuss the efficacy and safety of pembrolizumab in these patients. Pembrolizumab has shown good control and the patients have had long progression-free survival with a high quality of life. Neither patient has experienced serious or grade 3-4 treatment-related adverse events. Pembrolizumab demonstrates activity in brain metastases in NSCLC patients with an acceptable safety profile. Thus, there may be a role for systemic immunotherapy in patients with untreated or progressive brain metastases.
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. [2022]Immunotherapy targeting the PD-1 axis has activity in several tumour types. We aimed to establish the activity and safety of the PD-1 inhibitor pembrolizumab in patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC).
Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment. [2022]Brain metastases are common in patients with metastatic melanoma. With increasing numbers of melanoma patients on anti-PD-1 therapy, we sought to evaluate the safety and initial response of brain metastases treated with concurrent pembrolizumab and radiation therapy.
Melanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment. [2022]The role of immunotherapy in treatment of brain metastases is unknown because most trials exclude patients with active brain lesions. As new immunomodulating agents gain approval for many malignancies, it is important to know if they have unique effects in the central nervous system (CNS). Here, we present a case of a patient with progressing brain metastases treated with a single cycle of pembrolizumab, who presented with mental status changes 11 days thereafter. MRI of the brain showed enlargement of CNS lesions with intense central enhancement and diffuse perilesional edema. Histologic evaluation of a resected lesion revealed isolated clusters of tumor cells surrounded by reactive astrocytosis, scattered inflammatory cells, and an abundance of microglial cells. Given the increasing use of immune checkpoint inhibitors in patients with brain metastases from melanoma and other diseases, recognition of pseudoprogression and management with immune suppression are essential.
Rapid remission of symptomatic brain metastases in melanoma by programmed-death-receptor-1 inhibition. [2018]Although ∼40% of patients with metastatic melanoma develop brain metastases, the presence of brain metastases often precludes enrolment in clinical trials for advanced melanoma. However, the development of symptomatic brain metastases markedly increases mortality. The antiprogrammed-death-receptor-1 antibody pembrolizumab achieves extracranial metastases disease response rates of up to 50%. Here, we report the rapid and sustained response of symptomatic multifocal brain metastases in a melanoma ipilimumab-pretreated patient under pembrolizumab, combined with high-dose dexamethasone therapy during the induction phase of therapy. Complete remission has been maintained for over 1 year of follow-up and has correlated with the response rate observed in the extracranial metastases. Radiological disease response was identified during the first follow-up visit in the absence of adjuvant radiotherapy. This report highlights the need for further clinical studies to specifically address the therapeutic potential of antiprogrammed-death-receptor-1 monotherapy in the management of untreated brain metastases in melanoma.
Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. [2020]Pembrolizumab is active in melanoma, but activity in patients with untreated brain metastasis is less established. We present long-term follow-up of pembrolizumab-treated patients with new or progressing brain metastases treated on a phase II clinical trial ( ClinicalTrials.gov identifier: NCT02085070).