27 Participants Needed

Pembrolizumab for Recurrent Brain Cancer

Recruiting at 16 trial locations
TK
Overseen ByThomas Kaley, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test if the study drug called pembrolizumab could control the growth or shrink the cancer but it could also cause side effects. Researchers hope to learn if the study drug will shrink the cancer by half, or prevent it from growing for at least 6 months. Pembrolizumab is an antibody that targets the immune system and activates it to stop cancer growth and/or kill cancer cells.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on high doses of corticosteroids or have had certain treatments like anti-PD-1 agents before. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug pembrolizumab for treating brain cancer?

Pembrolizumab has shown effectiveness in treating various cancers, including non-small cell lung cancer and melanoma, by improving survival rates. It has also been studied for its activity in patients with brain metastases, suggesting potential benefits for brain cancer treatment.12345

Is pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been approved for use in several cancers, including melanoma and lung cancer. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects can affect the lungs, liver, and thyroid. Overall, its benefits in treating life-threatening conditions have been found to outweigh these risks.12467

What makes the drug pembrolizumab unique for treating recurrent brain cancer?

Pembrolizumab is unique because it is an immunotherapy drug that works by blocking the PD-1 pathway, which helps the immune system attack cancer cells. This mechanism is different from traditional chemotherapy, which directly targets and kills cancer cells, and it has shown promise in treating various cancers, including those with brain metastases.24589

Research Team

TK

Thomas Kaley, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with recurrent malignant glioma and a hypermutator phenotype, who've had prior treatments including radiation and chemotherapy. They must have stable vital functions, no severe allergies to pembrolizumab components, no active infections or autoimmune diseases requiring recent treatment, not be pregnant or breastfeeding, agree to contraception use during the study period, and cannot have received certain other cancer drugs before.

Inclusion Criteria

Tumor recurrence after previous treatment, which must have included at least radiation therapy and one cytotoxic chemotherapy. There is no limit on number of previous recurrences or lines of treatment.
Be willing and able to provide written informed consent/assent for the trial.
Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
See 44 more

Exclusion Criteria

Hypersensitivity to pembrolizumab or any of its excipients.
Has a diagnosis of immunodeficiency, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS)
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg as an IV infusion every 3 weeks. Patients will be followed with DCE perfusion MRI done at baseline and every 9 weeks.

27 weeks
Infusion every 3 weeks, MRI every 9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with radiologic assessments using MRI scans.

1 year

Treatment Details

Interventions

  • Pembrolizumab
Trial Overview The trial is testing pembrolizumab's effectiveness on brain tumors that recur after standard treatments. It aims to see if this drug can shrink tumors by at least half or prevent growth for six months. Pembrolizumab works by activating the immune system against cancer cells.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Pembrolizumab (MK-3475)Experimental Treatment1 Intervention
Pembrolizumab 200 mg will be administered as an approximately 30 minute (-5/+10 mins) IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. Patients will be followed with DCE perfusion MRI done at baseline and every 9 weeks (+/- 7 days). Patients will be allowed to stay on treatment in spite of increase in tumor size, provided the patient has no, or manageable, new neurologic symptoms, and at the discretion of treating physician. In that situation, tumor resection should be encouraged for the distinction between tumor progression and immunologic reactions. Patients undergoing surgical resection will have tissue collected for collateral studies. All collected tissue will be stored in the Pathology Core Tissue bank at MSK.

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

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Huntsman Cancer Institute/ University of Utah

Collaborator

Trials
2
Recruited
3,400+

University of California, San Francisco

Collaborator

Trials
2,636
Recruited
19,080,000+

M.D. Anderson Cancer Center

Collaborator

Trials
3,107
Recruited
1,813,000+

University of California, Los Angeles

Collaborator

Trials
1,594
Recruited
10,430,000+

Dana-Farber Cancer Institute

Collaborator

Trials
1,128
Recruited
382,000+

University of Miami

Collaborator

Trials
976
Recruited
423,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

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

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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

Findings from Research

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.
In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond.Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]
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.
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]
In a phase 2 trial involving 42 patients with untreated brain metastases from non-small-cell lung cancer (NSCLC), pembrolizumab showed a 29.7% response rate in patients with PD-L1 expression of at least 1%, indicating its efficacy in treating brain metastases.
The treatment was generally safe, with serious adverse events occurring in 14% of patients, but no treatment-related deaths were reported, suggesting that pembrolizumab can be a viable option for selected patients with CNS involvement.
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.Goldberg, SB., Schalper, KA., Gettinger, SN., et al.[2021]

References

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]
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]
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]
Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. [2020]
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]
FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]
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]