Pembrolizumab for Recurrent Brain Cancer

Not currently recruiting at 16 trial locations

Overseen By Thomas Kaley, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Corticosteroids, Anti-PD-1, Anti-CTLA-4, others

Disqualifiers: Immunodeficiency, Hepatitis, Active TB, 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

Duration: 27 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, a drug that helps the immune system fight cancer, to determine if it can shrink or control the growth of recurrent brain cancer. Researchers aim for it to stop tumors from growing for at least six months or even reduce their size by half. Individuals whose brain cancer has returned after treatments like radiation and chemotherapy, and whose tumor samples show many genetic changes, might be suitable for this trial.

As an unphased trial, this study provides a unique opportunity for patients to contribute to groundbreaking research that could lead to new treatment options.

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.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab is generally safe for treating certain cancers, including brain cancers. In past studies, pembrolizumab, a medicine that helps the immune system fight cancer, was well-tolerated by patients. Some side effects were reported, but they were usually manageable.

One study focused on pembrolizumab for brain cancer and found it generally safe for patients. While some side effects occurred, the treatment did not cause unexpected safety issues. Common side effects might include fatigue or skin reactions, but serious side effects are rare.

Although the FDA has approved pembrolizumab for other types of cancer, researchers continue to study its effects on brain cancer. Its approval for other uses suggests confidence in its overall safety. However, individuals considering clinical trials should discuss potential risks and benefits with their healthcare team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it harnesses the power of the immune system to target brain cancer cells. Unlike traditional treatments like chemotherapy, which can affect both healthy and cancerous cells, pembrolizumab works by blocking the PD-1 pathway, effectively taking the brakes off the immune system to allow it to attack cancer cells more effectively. This immunotherapy approach offers a new mechanism of action that could lead to better outcomes for patients with recurrent brain cancer, making it a promising option in the fight against this challenging condition. Researchers are excited about pembrolizumab because it represents a shift towards more targeted, personalized cancer treatments with potentially fewer side effects.

What evidence suggests that pembrolizumab might be an effective treatment for recurrent brain cancer?

Research has shown that pembrolizumab, the treatment under study in this trial, can assist with certain types of recurring brain cancer. In some studies, 50% of patients with recurrent glioblastoma, a type of brain cancer, experienced stable disease or better outcomes. Another study found that patients treated with pembrolizumab lived longer, with an average survival time of 10.2 months. Pembrolizumab aids the immune system in attacking cancer cells, potentially stopping the cancer from growing or even shrinking it. While these results are promising, effectiveness can vary, and not everyone may experience the same outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Thomas Kaley, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

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).

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Pembrolizumab (MK-3475) Experimental Treatment 1 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

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

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

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

Published Research Related to This Trial

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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 clinical trial involving 23 melanoma patients with untreated brain metastases, pembrolizumab demonstrated a 26% response rate in brain metastases, indicating its potential efficacy in this challenging patient population.

The treatment was associated with acceptable toxicity, as 65% of patients experienced neurologic adverse events, mostly mild (grade 1 or 2), and nearly half of the patients (48%) were alive at 24 months, suggesting durable responses and a need for careful management of brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. Kluger, HM., Chiang, V., Mahajan, A., et al.[2020]

In a phase 2 trial involving 36 patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC), pembrolizumab demonstrated activity, achieving a brain metastasis response in 22% of melanoma patients and 33% of NSCLC patients, with responses being durable for most.

The treatment had an acceptable safety profile, with serious adverse events occurring in a small percentage of patients, indicating that systemic immunotherapy could be a viable option for those with untreated or progressive brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Goldberg, SB., Gettinger, SN., Mahajan, A., 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) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[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]

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