Virus Therapy for Brain Tumors

Overseen By Frederick Lang

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Pregnancy, Infection, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: 2

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking other cytotoxic and non-cytotoxic drugs or radiation therapy against the tumor while enrolled. Additionally, there are specific time periods that must be observed after completing certain chemotherapies before starting the trial.

What data supports the effectiveness of the treatment DNX-2401 for brain tumors?

Research shows that DNX-2401, an oncolytic virus, can help some patients with brain tumors live longer by directly attacking tumor cells and boosting the body's immune response against the tumor. In studies, some patients with recurrent malignant glioma experienced significant tumor reduction and long-term survival, and the treatment was found to be safe in both adults and children. ^{1 2 3 4 5}

Is DNX-2401 safe for use in humans?

DNX-2401 has been tested in clinical trials for brain tumors and has shown a favorable safety profile, with no dose-limiting toxicities reported. It has been well tolerated in both adults and children, with some patients experiencing long-term survival. ^{1 2 3 4 6}

What makes the treatment DNX-2401 unique for brain tumors?

DNX-2401 is unique because it is an oncolytic virus, meaning it is a virus designed to selectively infect and kill cancer cells while sparing normal cells. It works by directly destroying tumor cells and stimulating the body's immune system to attack the tumor, offering a novel approach compared to traditional treatments like chemotherapy or radiation. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase I trial studies best dose and side effects of oncolytic adenovirus DNX-2401 in treating patients with high-grade glioma that has come back (recurrent). Oncolytic adenovirus DNX-2401 is made from the common cold virus that has been changed in the laboratory to make it less likely to cause an infection (such as a cold). The virus is also changed to target brain cancer cells and attack them.

Research Team

Frederick F Lang

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with recurrent high-grade glioma, such as glioblastoma or astrocytoma, who have tried surgery, chemotherapy, or radiation before. They must be in good enough health to undergo endovascular treatment and have a life expectancy of at least 16 weeks. Participants need a tumor size between 1-5 cm and a Karnofsky score ≥70 (able to care for themselves). Pregnant women are excluded.

Inclusion Criteria

My tumor can be removed surgically, and I need a surgery to remove part of my skull to access it.

My recurrent brain tumor does not have IDH-1 mutation and shows a significant mass on MRI.

It has been at least 8 weeks since my last radiotherapy session.

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

I have trouble getting IV lines placed for procedures.

I haven't had biologic or immunotherapy in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part I

Patients receive one or two infusions of BM-hMSCs-DNX-2401 intra-arterially over 20-30 minutes on day 0. Dose level 1-5 will receive 1 infusion. Dose level 6 will receive 2 infusions.

1 day

1 visit (in-person)

Treatment Part II

Patients receive one or two infusions of BM-hMSCs-DNX-2401 IA, depending on the highest dose tolerated in Part 1. After 2 weeks, patients undergo surgery where the tumor is removed, then receive intramural injection of BM-hMSCs-DNX-2401 into the resection cavity.

2 weeks

1 visit (in-person) for surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs on days 1, 4, 7, and 14 of month 1, every 6 weeks for 6 months, then every 8 weeks for 1 year, then every 4 months for 1 year, then every 6 months until the tumor grows back.

Up to 2 years

Multiple visits (in-person)

Treatment Details

Interventions

• DNX-2401

Trial Overview The trial is testing the safety and optimal dose of DNX-2401, an altered cold virus targeting brain cancer cells. It's given after conventional surgery to see if it can help treat recurrent high-grade gliomas more effectively than current treatments.

Participant Groups

Group I: Part II (oncolytic adenovirus Ad5-DNX-2401, surgery) Experimental Treatment 2 Interventions

Patients receive oncolytic adenovirus Ad5-DNX-2401 as in part I. After 2 weeks, patients undergo surgery, then receive oncolytic adenovirus Ad5-DNX-2401 IA over 20-30 minutes.

Group II: Part I (oncolytic adenovirus Ad5-DNX-2401) Experimental Treatment 1 Intervention

Patients receive oncolytic adenovirus Ad5-DNX-2401 IA over 20-30 minutes on day 0.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

DNAtrix, Inc.

Industry Sponsor

Trials

8

Recruited

250+

Findings from Research

In a phase I clinical trial involving 37 patients with recurrent malignant glioma, DNX-2401 demonstrated significant efficacy, with 20% of patients surviving over 3 years and three patients experiencing a greater than 95% reduction in tumor size.

The treatment not only caused direct oncolysis of tumor cells but also triggered an immune response, as evidenced by increased infiltration of immune cells and signs of immunogenic cell death, suggesting a dual mechanism of action for DNX-2401.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. Lang, FF., Conrad, C., Gomez-Manzano, C., et al.[2023]

In a multicenter phase 1/2 study involving 49 patients with recurrent glioblastoma, the combination of the oncolytic virus DNX-2401 and the anti-PD-1 antibody pembrolizumab was found to be safe, with no dose-limiting toxicities and good tolerability.

While the objective response rate was 10.4%, which did not exceed the control rate, the treatment showed a significant overall survival benefit at 12 months (52.7%), indicating that this combination may be effective for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. Nassiri, F., Patil, V., Yefet, LS., et al.[2023]

DNX-2401, an oncolytic adenovirus, has shown a favorable safety profile in adults with glioblastoma and is being tested in a Phase I trial for pediatric patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPG), which currently have no curative treatment.

The first case report of an 8-year-old patient receiving intratumoral DNX-2401 after a biopsy indicated no safety concerns or neurological deficits, suggesting that this approach may be a feasible and innovative treatment option for DIPG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report. Tejada, S., Díez-Valle, R., Domínguez, PD., et al.[2020]

Delta-24-based oncolytic viruses, specifically DNX-2401, have shown promising clinical responses in a phase I trial for recurrent glioblastoma, with some patients experiencing long-term benefits and minimal toxicity.

The therapy appears to enhance immune infiltration in tumors, suggesting that it may not only target cancer cells directly but also stimulate an antitumor immune response, paving the way for further research and potential phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta-24 adenoviral therapy for glioblastoma: evolution from the bench to bedside and future considerations. Ene, CI., Fueyo, J., Lang, FF.[2021]

The oncolytic virus Delta-24-RGD has been shown to be safe and significantly increase survival in mouse models of pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs), indicating its potential as a treatment option.

The therapeutic effect of Delta-24-RGD is attributed to both its ability to directly kill tumor cells and to stimulate an immune response against the tumors, leading to the initiation of a phase I/II clinical trial for newly diagnosed DIPG patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models. Martínez-Vélez, N., Garcia-Moure, M., Marigil, M., et al.[2021]

A phase 1 clinical trial of the oncolytic adenovirus Delta-24-RGD in pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) showed it is feasible and has an acceptable safety profile, indicating it could be a promising treatment option.

The study also demonstrated encouraging efficacy results, suggesting that Delta-24-RGD may trigger a biological response in DIPG, especially when combined with standard radiotherapy, warranting further advanced trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic virotherapy for the treatment of pediatric brainstem gliomas. Gállego Pérez-Larraya, J., García-Moure, M., Alonso, MM.[2023]

References

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

Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. [2023]

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

Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. [2023]

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

DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report. [2020]

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

Delta-24 adenoviral therapy for glioblastoma: evolution from the bench to bedside and future considerations. [2021]

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

The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Oncolytic virotherapy for the treatment of pediatric brainstem gliomas. [2023]