Pembrolizumab + Vaccine for Glioblastoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Timothy F Cloughesy, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Pregnancy, Autoimmune disease, Active infection, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of an immunotherapy drug, pembrolizumab, and a vaccine, ATL-DC, in patients with recurrent glioblastoma that can be surgically removed. The goal is to see if this combination can help the immune system better attack the cancer and improve patient outcomes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not be on certain therapies like systemic steroids or immunosuppressive drugs within 7 days before starting the study treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Pembrolizumab + Vaccine for Glioblastoma?

Research shows that dendritic cell vaccines, like the ATL-DC vaccine used in this treatment, have been associated with increased survival in glioblastoma patients. Additionally, studies indicate that these vaccines generally have mild side effects and can improve immune responses against tumors. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and a vaccine safe for treating glioblastoma?

Pembrolizumab, used in various conditions including glioblastoma and lung cancer, has been shown to be safe in clinical trials. Dendritic cell vaccines, like those used for glioblastoma, have also demonstrated safety in early trials, with no significant toxic effects reported. ^{1 3 6 7 8}

What makes the Pembrolizumab + Vaccine treatment for glioblastoma unique?

This treatment combines pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with a vaccine designed to target glioblastoma cells specifically, offering a novel approach compared to standard treatments that often have limited effectiveness. ^{1 2 6 9 10}

Research Team

Timothy F Cloughesy, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with recurrent glioblastoma that can be surgically removed. They must have a tumor of a certain size, not be on immunosuppressive therapy, and agree to use contraception. Excluded are pregnant or breastfeeding women, those with recent other cancer treatments or live vaccines, severe allergies to pembrolizumab, active infections like HIV or hepatitis B/C, and autoimmune diseases treated within the last 2 years.

Inclusion Criteria

My liver function tests are within the required range.

I am eligible for a surgery to remove at least 2 grams of my tumor safely.

It's been over 12 weeks since my last radiotherapy, or I have confirmed tumor growth since then.

Exclusion Criteria

I have recovered from any major surgery before starting the study treatment.

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

You have a severe allergic reaction (grade 3 or higher) to pembrolizumab or any of its ingredients.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Patients receive pembrolizumab or placebo intravenously 14 days prior to scheduled surgery

2 weeks

1 visit (in-person)

Surgery

Surgical resection of recurrent glioblastoma

1 day

1 visit (in-person)

Adjuvant Treatment

Post-surgery, patients receive pembrolizumab or placebo every 3 weeks and ATL-DC with poly ICLC every 2 weeks for up to 3 doses

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

Every 3 months

Treatment Details

Interventions

• ATL-DC Vaccine (Cancer Vaccine)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The trial tests how well pembrolizumab (an antibody) works alongside an ATL-DC vaccine in treating recurrent glioblastoma compared to the vaccine alone. The study aims to see if this combination helps the immune system better attack cancer cells and prevent their growth.

Participant Groups

Group I: Group A (pembrolizumab, ATL-DC, poly ICLC) Experimental Treatment 3 Interventions

Beginning 14 days prior to scheduled surgery, patients receive pembrolizumab IV over 30 minutes. After surgery, patients receive pembrolizumab IV over 30 minutes on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

Group II: Group B (placebo, ATL-DC, poly ICLC) Active Control 3 Interventions

Beginning 14 days prior to scheduled surgery, patients receive placebo IV. After surgery, patients receive placebo IV on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Dr. Aparna Bhaduri

Jonsson Comprehensive Cancer Center

Chief Medical Officer since 2024

MD

Dr. Michael A. Teitell

Jonsson Comprehensive Cancer Center

Chief Executive Officer since 2024

MD, PhD

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

Phase One Foundation

Collaborator

Trials

5

Recruited

180+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Oncovir, Inc.

Industry Sponsor

Trials

25

Recruited

680+

Findings from Research

The AV-GBM-1 vaccine was successfully manufactured for all 63 patients in the trial, demonstrating a high success rate of 97% for tumor cell production and monocyte collection, which is crucial for its effectiveness.

While the treatment was generally well-tolerated, with common side effects including local injection reactions and flu-like symptoms, it also led to significant central nervous system adverse events, such as seizures and headaches, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment. Bota, DA., Taylor, TH., Piccioni, DE., et al.[2023]

In a study of 26 patients with recurrent glioblastoma, pembrolizumab showed an overall response rate of 8%, with two patients experiencing partial responses lasting up to 22.8 months, indicating some durable antitumor activity.

While 73% of patients experienced treatment-related adverse events, most were manageable, suggesting that pembrolizumab has a safety profile that allows for further exploration in combination therapies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Reardon, DA., Kim, TM., Frenel, JS., et al.[2021]

Dendritic cell (DC) vaccination has been shown to be safe and non-toxic in early phase trials for treating glioblastoma multiforme (GBM), suggesting a promising new immunotherapy approach.

Pre-clinical studies in mice demonstrated that DCs loaded with glioblastoma proteins significantly increased survival rates, supporting the potential for clinical trials in patients with GBM who do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice. Pellegatta, S., Poliani, PL., Corno, D., et al.[2006]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment. [2023]

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

DCVax®-L--developed by Northwest Biotherapeutics. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Advances and challenges: dendritic cell vaccination strategies for glioblastoma. [2021]

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

Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients. [2021]

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

Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients. [2021]

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

Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice. [2006]

8. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. [2021]

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

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. [2022]