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

Trial Summary

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.

What makes the drug MVR-C5252 unique for treating brain tumors?

MVR-C5252 is unique because it may involve a novel mechanism of action or specific targeting of molecular alterations in brain tumors, which is different from standard treatments like surgery, radiotherapy, or chemotherapy. This approach could potentially enhance the immune response against tumor cells, offering a new avenue for treatment where traditional methods have limited effectiveness. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a Phase 1 open label study designed to assess the safety and tolerability of the oncolytic herpes simplex virus 1 (oHSV1) study drug, MVR-C5252, administered intratumorally by convection-enhanced delivery (CED) in patients with recurrent high-grade glioma. Once the safety and maximum tolerated dose (MTD) is established in the dose escalation portion of the trial, a dose expansion cohort at the recommended phase 2 dose (RP2D) in patients with isocitrate dehydrogenase (IDH) wildtype recurrent glioblastoma (GBM) will evaluate preliminary efficacy of the study drug.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

GITRL-armed Delta-24-RGD oncolytic adenovirus prolongs survival and induces anti-glioma immune memory. [2022]

2. United States 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. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Therapies in Rare Brain Tumours. [2021]

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

Expression of MAGE and GAGE in high-grade brain tumors: a potential target for specific immunotherapy and diagnostic markers. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. [2022]