Immunotherapy for Brain Cancer

Recruiting at 6 trial locations

Overseen By Kathryn Partridge

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, Anti-angiogenics

Disqualifiers: Immunodeficiency, Active infection, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

60 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like high-dose corticosteroids or recent investigational agents may affect eligibility, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment MK-3475 for brain cancer?

Immunotherapy, which includes treatments like MK-3475, has shown promise in treating brain tumors by helping the immune system attack cancer cells. Although specific data on MK-3475 for brain cancer is not provided, similar immunotherapy approaches have shown encouraging results in clinical trials for brain tumors, suggesting potential effectiveness. ^{1 2 3 4 5}

Is MK-3475 safe for humans?

The research articles provided do not contain specific safety data for MK-3475, but they do mention other compounds with similar naming conventions, such as MK-462 and MK-571, which were generally well tolerated in human studies. However, this information may not directly apply to MK-3475. ^{6 7 8 9 10}

How does the drug MK-3475 differ from other treatments for brain cancer?

MK-3475, also known as pembrolizumab, is an immunotherapy drug that works by blocking a protein called PD-1 on immune cells, which helps the immune system attack cancer cells more effectively. This mechanism is different from traditional treatments like chemotherapy, which directly kill cancer cells, and it offers a novel approach by enhancing the body's own immune response against brain cancer. ^{1 2 11 12 13}

What is the purpose of this trial?

This research study is studying an immunotherapy as a possible treatment for Glioblastoma.

Research Team

Patrick Wen, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with Grade IV malignant glioma (glioblastoma or gliosarcoma) who have undergone initial treatment and are at their first or second relapse. Participants must be over 18, able to consent, have a performance status indicating they can carry out daily activities, and show tumor progression on scans. They should also have normal organ function as defined by the study's criteria.

Inclusion Criteria

Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.

My brain tumor is confirmed as a high-grade glioma (glioblastoma or gliosarcoma).

My cancer has returned once or twice after treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Pre-surgery Treatment

Pembrolizumab (MK-3475) administered pre-surgery at a predetermined dosage

2 weeks

1 visit (in-person)

Post-surgery Treatment

Pembrolizumab (MK-3475) administered every 3 weeks post-surgery

6 months

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• MK-3475

Trial Overview The trial is testing Pembrolizumab (MK-3475), an immunotherapy drug, in patients with recurrent/progressive Glioblastoma that can be accessed surgically. It aims to understand how this drug affects early immune responses against the tumor.

Participant Groups

Group I: Pre-surgery MK-3475 Experimental Treatment 1 Intervention

-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK3475) pre-surgery at pre-determine dosage followed by Pembrolizumab at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously

Group II: No MK-3475 at Pre-Surgery Active Control 1 Intervention

-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK-3475) at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

Findings from Research

Malignant brain tumors remain difficult to treat, with long-term survival only improving from 6 to 15 months over the last 80 years, despite advancements in surgery, chemotherapy, and radiotherapy.

Immunotherapy, particularly using immune modulators like CTLA-4 and PD-1/PD-L1, is being actively researched in ongoing phase I and III trials, showing promise in targeting glioma antigens, but challenges remain in achieving complete responses and understanding the lack of adverse brain inflammation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of EGFRvIII as the target for glioma vaccines. Lowenstein, PR., Castro, MG.[2021]

Intravenous doses of MK-462 ranging from 5 to 90 micrograms per kg were found to be well tolerated in healthy males, with linear pharmacokinetics observed for doses up to 60 micrograms per kg.

Food intake prior to oral administration of MK-462 increased its overall exposure (AUC) by about 20% but did not significantly affect peak concentration (Cmax) or half-life (t1/2), indicating that MK-462 can be taken with or without food without major impacts on its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and food interaction of MK-462 in healthy males. Cheng, H., Polvino, WJ., Sciberras, D., et al.[2012]

MK-8389 was found to be generally safe and well tolerated in healthy young women over a 14-day period, although it caused transient changes in thyroid function tests that limited dose escalation above 40 mg.

While MK-8389 showed acceptable systemic exposure, it did not have a clinically meaningful effect on follicular development, although higher doses did increase inhibin B levels, indicating some early follicular activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function. Gerrits, MG., Kramer, H., el Galta, R., et al.[2016]

MK-571, a leukotriene D4 receptor antagonist, was well tolerated in both intravenous and oral forms, with no serious side effects reported, even at high doses up to 1500 mg.

The study showed that MK-571 is rapidly absorbed when taken orally, with peak plasma concentrations reached within 1-2 hours, and a modest accumulation of the drug in plasma over multiple doses, indicating its potential for effective long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma drug profiles and tolerability of MK-571 (L-660,711), a leukotriene D4 receptor antagonist, in man. Depré, M., Margolskee, DJ., Hsieh, JY., et al.[2019]

MK-801 significantly reduces brain lesion volume and cerebral edema in rat models of acute brain injury, based on a systematic review of 52 studies involving 2530 samples.

The treatment with MK-801 also improves neurological function and spatial cognition, indicating its potential as a neuroprotective agent with a favorable safety profile for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis. Yi, NX., Zhou, LY., Wang, XY., et al.[2022]

The INTERCEPT H3 trial is investigating the safety and immunogenicity of the H3K27M-vac vaccine in combination with standard radiotherapy and the immune checkpoint inhibitor atezolizumab in 15 adult patients with newly diagnosed diffuse midline gliomas (DMG) carrying the H3K27M mutation.

Preliminary results from earlier studies suggest that the H3K27M-vac vaccine can induce specific immune responses that may help suppress tumor growth, making it a promising treatment strategy for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas. Grassl, N., Sahm, K., Süße, H., et al.[2023]

The H3.3K27M-targeted peptide vaccine was well tolerated in patients with diffuse midline gliomas, with no severe treatment-related adverse events reported, indicating a favorable safety profile.

Patients who developed H3.3K27M-reactive CD8+ T cell responses had a significantly longer overall survival (median OS of 16.1 months) compared to those who did not respond, highlighting the potential efficacy of the vaccine in improving outcomes for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma. Mueller, S., Taitt, JM., Villanueva-Meyer, JE., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Anti-KIR Antibody of 1-7F9 Attenuates the Antitumor Effects of Expanded and Activated Human Primary Natural Killer Cells on In Vitro Glioblastoma-like Cells and Orthotopic Tumors Derived Therefrom. [2023]

2. France pubmed.ncbi.nlm.nih.gov

The cellular immunotherapy of primary brain tumors. [2005]

3. United States pubmed.ncbi.nlm.nih.gov

The value of EGFRvIII as the target for glioma vaccines. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Natural killer cell-related gene signature predicts malignancy of glioma and the survival of patients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Toward effective immunotherapy for the treatment of malignant brain tumors. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and food interaction of MK-462 in healthy males. [2012]

7. United States pubmed.ncbi.nlm.nih.gov

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function. [2016]

8. Germany pubmed.ncbi.nlm.nih.gov

Plasma drug profiles and tolerability of MK-571 (L-660,711), a leukotriene D4 receptor antagonist, in man. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Interruption of functional recovery by the NMDA glutamate antagonist MK801 after compression of the sensorimotor cortex: implications for treatment of tumors or other mass-related brain injuries. [2018]

10. India pubmed.ncbi.nlm.nih.gov

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis. [2022]

11. England pubmed.ncbi.nlm.nih.gov

INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Bi-Specific Killer Cell Engager Enhances NK Cell Activity against Interleukin-13 Receptor Alpha-2 Positive Gliomas. [2023]