MVR-C5252 for Brain Tumors

(PuMP Trial)

Overseen By Monika Anand, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Duke University

Must be taking: Radiation, Temozolomide

Must not be taking: Immunosuppressants, Antiangiogenics, Anti-HSV, others

Disqualifiers: Pregnancy, Active infection, Cardiac risks, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a new treatment, MVR-C5252, for individuals with recurrent high-grade glioma, a type of brain tumor. This treatment uses a specially engineered virus to target and attack the tumor directly. The trial seeks participants with a recurring tumor that has not responded to standard treatments. As a Phase 1 trial, participants will be among the first to receive this innovative treatment, helping researchers understand its effects in people.

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

The trial does not specify if you need to stop all current medications, but you cannot take more than 4 mg of dexamethasone daily within 2 weeks before the trial or use certain cancer treatments and vaccines close to the trial start. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that MVR-C5252 is likely to be safe for humans?

Research has shown that MVR-C5252 is under study to assess its safety and patient tolerance. This treatment uses a virus called oHSV1, injected directly into brain tumors. Convection-enhanced delivery (CED) helps the virus reach the tumor while minimizing effects on the rest of the body.

Early results from other studies of MVR-C5252 indicate that patients generally tolerate it well, with side effects usually not severe for most people. As this trial is in the early stages, the main goal is to determine the right dose that is both safe and effective.

The FDA has approved testing this treatment in people, suggesting some confidence in its potential safety. However, as this is a new treatment, researchers continue to monitor for any unexpected issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for brain tumors, which often involve surgery, radiation, or chemotherapy, MVR-C5252 introduces a novel approach by using genetically engineered oncolytic herpes simplex viruses. This treatment is unique because it employs a delivery method called Convection-enhanced delivery (CED), which allows the drug to bypass the blood-brain barrier and be delivered directly into the tumor, minimizing systemic side effects. Researchers are excited about MVR-C5252 because its targeted action could potentially offer a more effective and less toxic alternative to current treatment options.

What evidence suggests that MVR-C5252 might be an effective treatment for brain tumors?

Research has shown that MVR-C5252, a type of modified herpes virus, may help treat brain tumors like recurrent high-grade glioma. This treatment attacks and destroys cancer cells while sparing healthy ones. Participants in this trial will receive MVR-C5252 directly into the tumor. Early studies suggest this approach can effectively bypass the blood-brain barrier, a common challenge in treating brain cancer. Although still in early stages, this method aims to shrink the tumor and slow the disease's progression. Initial trials indicated that MVR-C5252 might be safe and tolerable, offering hope for its potential to combat aggressive brain tumors. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent high-grade glioma, specifically IDH wildtype glioblastoma. Participants must have tried standard treatments without success and meet specific health and tumor location criteria.

Inclusion Criteria

My cancer is within or near an area of increased growth.

My condition is at least 0.5 cm away from the brain's ventricles.

My tumor is at least 0.5 cm away from the corpus callosum.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Single administration of MVR-C5252 via externalized Synchromed II pump

4 weeks

1 visit (in-person)

Stage 2 Treatment

Two infusions of MVR-C5252 on days 1 and 28 via internalized pump

8 weeks

2 visits (in-person)

Stage 3 Treatment

Six cycles of two infusions each, with the second infusion occurring 7 ± 1 days after the first

12 weeks

12 visits (in-person)

Stage 4 Dose Expansion

Evaluation of efficacy at the recommended phase 2 dose (RP2D)

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• MVR-C5252

Trial Overview The study tests MVR-C5252, an oncolytic virus therapy injected directly into the brain tumor. It aims to find a safe dose and see if it's effective against aggressive brain tumors in two phases: dose escalation and expansion.

How Is the Trial Designed?

Group I: MVR-C5252 Experimental Treatment 1 Intervention

Open label single arm infusion of MVR-C5252, genetically engineered type 1 oHSV (oncolytic herpes simplex viruses) into the tumor via Convection-enhanced delivery (CED) a modality that can bypass the BBB (Blood Brain Barrier), allowing the intracranial delivery through the BBB and avoiding systemic toxicities.

MVR-C5252 is already approved in China, United States for the following indications:

Approved in China as MVR-C5252 for:

• Malignant glioma

Approved in United States as MVR-C5252 for:

• Recurrent high-grade glioma
• Isocitrate dehydrogenase (IDH) wildtype recurrent glioblastoma (GBM)

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

The experimental EGFRvIII-targeted peptide vaccine successfully induced immune responses in patients with glioblastoma multiforme (GBM) undergoing treatment with temozolomide (TMZ), even in the presence of chemotherapy-induced lymphopenia.

Patients receiving the dose-intensified TMZ regimen showed greater immune responses and significantly improved median progression-free survival (15.2 months) and overall survival (23.6 months) compared to historical controls, indicating the vaccine's efficacy in targeting tumor cells without causing autoimmunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. Sampson, JH., Aldape, KD., Archer, GE., et al.[2022]

Delta-24-GREAT, a modified version of Delta-24-RGD armed with the GITRL ligand, effectively infects glioma cells and enhances the immune response against gliomas, leading to prolonged survival in mice with glioma.

The treatment not only generated specific antitumor immunity but also established long-term immune memory, as evidenced by the lack of tumor growth upon re-exposure to glioma cells, indicating its potential as a targeted therapy for malignant brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GITRL-armed Delta-24-RGD oncolytic adenovirus prolongs survival and induces anti-glioma immune memory. Rivera-Molina, Y., Jiang, H., Fueyo, J., et al.[2022]

Recent advancements in molecular techniques have identified actionable alterations in rare CNS tumors, leading to potential targeted therapies that can improve neurological symptoms and quality of life.

Specific treatments targeting pathways like mTOR in SEGAs and BRAF V600E mutations in certain glial and glioneuronal tumors show promise, highlighting the importance of personalized medicine in managing these challenging conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapies in Rare Brain Tumours. Bruno, F., Pellerino, A., Bertero, L., et al.[2021]

The study analyzed mRNA expression of tumor-associated antigens MAGE and GAGE in 60 high-grade brain tumors, revealing that GAGE-1 is absent in normal brain tissue but frequently expressed in tumors, suggesting it could be a promising target for immunotherapy.

The methods used, including reverse transcription-PCR and Southern blotting, not only help identify these tumor markers but also provide a rapid screening tool for diagnosing brain tumors and determining eligibility for targeted immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of MAGE and GAGE in high-grade brain tumors: a potential target for specific immunotherapy and diagnostic markers. Scarcella, DL., Chow, CW., Gonzales, MF., et al.[2020]

A study of 159 patients with grade II/III gliomas revealed significant over-expression of specific tumor-associated antigens (BCAN, CSPG4, IGF2BP3, PTPRZ1, and TNC) at both mRNA and protein levels, indicating their potential as targets for immunotherapy.

In a smaller group of 27 patients, spontaneous T cell responses to the IMA950 antigens were detected in all grade II patients and 71% of grade III patients, suggesting that these antigens are relevant for effective tumor targeting and could enhance the efficacy of immunotherapy when combined with other peptides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma. Dutoit, V., Migliorini, D., Ranzanici, G., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06126744

NCT06126744 | Open-Label Study to Evaluate the Safety, ... This study is investigating if oHSV1 MVR-C5252 administered via CED can overcome the BBB (Blood Brain Barrier) in patients with recurrent high-grade glioma.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-05811

MVR-C5252 for the Treatment of Patients with Recurrent ... Giving MVR-C5252 may be safe, tolerable, and/or effective in treating patients with recurrent high-grade gliomas.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05095441

NCT05095441 | A Clinical Study of Intratumoral MVR- ... This is a Phase 1 open label, first in human study of C5252 monotherapy designed to determine the safety and tolerability of a single intratumoral (IT) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9958853/

Recent Developments in Glioblastoma Therapy: Oncolytic ... Here we review virotherapy for glioblastomas and describe several OVs and their combination with other therapies.

5. braintumor.org braintumor.org/news/new-brain-tumor-clinical-trials-april-october-2024/

New Brain Tumor Clinical Trials: April – October 2024 This is a phase I trial to assess the safety and tolerability of the oncolytic herpes simplex virus 1 (oHSV1) study drug, MVR-C5252, ...

6. immviragroup.com immviragroup.com/news/555.html

ImmVira's MVR-C5252 Targeting Brain Tumor Obtained US ... SHENZHEN, China, Aug. 8, 2021 /PRNewswire/ -- ImmVira announces MVR-C5252 targeting Glioblastoma has received the U.S. FDA clearance to proceed with ...

7. delta.larvol.com delta.larvol.com/Products/?ProductId=e36dc33b-e7b6-4671-9837-51887e8b5c1f

MVR-C5252 / ImmVira Pharma ImmVira Presented Clinical Results of Oncolytic Product MVR-C5252 Targeting Malignant Glioma via Convection-Enhanced Delivery at 2025 AACR Annual Meeting ...

8. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT056/761331/Abstract-CT056-A-phase-1-study-of-intratumoral

Abstract CT056: A phase 1 study of intratumoral HSV1 co ... This Phase 1 trial evaluates the safety, tolerability, and preliminary efficacy of MVR-C5252 delivered intratumorally via convection-enhanced delivery (CED).