DNX-2401 for Melanoma

Overseen By Christopher Alvarez-Breckenridge, MD, PHD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Immunotherapy

Must not be taking: High-dose corticosteroids, Anticoagulants

Disqualifiers: More than 5 brain metastases, Leptomeningeal disease, Uveal melanoma, Checkpoint inhibitor naïve, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DNX-2401 for individuals with advanced melanoma that has spread to other parts of the body, including the brain. The study aims to determine the optimal dose and number of DNX-2401 injections to manage this condition. Participants may receive the treatment directly into brain lesions or other cancerous areas. This trial suits those with stage IV melanoma who are not responding to standard treatments and have lesions that can be safely injected with DNX-2401. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Is there any evidence suggesting that DNX-2401 is likely to be safe for humans?

Research has shown that DNX-2401, a virus used to fight cancer, has been safe in earlier studies. When researchers injected DNX-2401 directly into the tumors of adults with recurring glioblastoma, a type of brain cancer, patients tolerated it well. These studies did not identify any major safety issues, indicating that DNX-2401 is generally safe for people. Additionally, combining DNX-2401 with another treatment, pembrolizumab, has been safe for some glioblastoma patients. Although more research is needed, the safety results for DNX-2401 remain promising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

DNX-2401 is unique because it uses a modified virus to target and destroy melanoma cells directly, offering a novel mechanism compared to traditional options like surgery, chemotherapy, and immunotherapy. Researchers are excited about its potential to selectively infect and kill cancer cells without harming normal tissues, which could lead to fewer side effects. Additionally, DNX-2401 is administered through direct injections into tumors, potentially making it more effective at reaching and treating specific lesions, including those in the brain, which are challenging for other treatments.

What evidence suggests that DNX-2401 might be an effective treatment for metastatic melanoma?

Research has shown that DNX-2401, a virus targeting cancer cells, can effectively kill these cells. In studies on glioblastoma, a type of brain cancer, DNX-2401 changed the tumor environment and helped combat the cancer. It was safely used with other treatments, such as pembrolizumab, which improved survival for some patients. Another study found that DNX-2401, when combined with temozolomide (a chemotherapy drug), was well tolerated and showed positive effects. Although these studies did not focus on melanoma, they suggest that DNX-2401 might help treat cancers by directly attacking tumor cells. Participants in this trial will receive DNX-2401 in different treatment arms, with varying dosages and delivery methods, to evaluate its effectiveness in treating melanoma. ^{2 4 6 7 8}

Who Is on the Research Team?

Christopher Alvarez-Breckenridge, MD, PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Inclusion Criteria

Patients must be able to complete an MRI of the head with contrast

I have been diagnosed with stage IV melanoma.

I am fully active or can do light work despite my illness.

Exclusion Criteria

I have a history of brain infections or diseases like encephalitis or multiple sclerosis.

I have taken more than 2mg of dexamethasone daily in the past week.

I have had a lymphoproliferative disorder in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DNX-2401 injections for metastatic melanoma, with up to 6 injections for Group B and up to 3 injections for Group A Arm 2

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of adverse events and antitumor activity

1 year

What Are the Treatments Tested in This Trial?

Interventions

• DNX-2401

How Is the Trial Designed?

Group I: GroupA-Arm1: IC virus delivery followed by surgical resection Experimental Treatment 1 Intervention

Participants will receive 1 injection of DNX-2401.

Group II: Group B: Patients with either EC or EC and IC disease Experimental Treatment 1 Intervention

Participants in Group B, you will receive up to 6 injections of DNX-2401.

Group III: Group A-Arm 2: DL1, DL2, DL3 Experimental Treatment 1 Intervention

Participants in Group A Arm 2, you will receive DNX-2401 at the recommended dose that was found in Group A Arm 1, and you will receive up to 3 injections of DNX-2401 into the selected brain lesion.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1.

nature.com

nature.com/articles/s41591-023-02347-y

Oncolytic DNX-2401 virotherapy plus pembrolizumab in ...

Existing salvage therapies have very limited efficacy, with median survival being in the range of only 6–8 months after tumor progression.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6075856/

Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic ...

These data demonstrate the ability of DNX-2401 to lyse glioma cells and provide evidence for active oncolytic adenovirus replication in human gliomas. Efficacy.

3.

mdanderson.org

mdanderson.org/newsroom/combined-delivery-engineered-virus-immunotherapy-safe-improves-outcomes-subset-patients-glioblastoma.h00-159618645.html

Combined delivery of engineered virus with ...

In previous Phase I trial results, DNX-2401 monotherapy effectively induced cancer cell death and changed the microenvironment to allow for ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37188783/

Oncolytic DNX-2401 virotherapy plus pembrolizumab in ...

The combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients.

5.

thejns.org

thejns.org/focus/view/journals/neurosurg-focus/50/2/article-pE6.pdf

Delta-24 adenoviral therapy for glioblastoma

13,15. Results of a phase I clinical trial for DNX-2401 (second generation) in recurrent glioblastoma have been reported7 and are discussed in the section below ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5858123/

DNX-2401, an Oncolytic Virus, for the Treatment of Newly ...

Clinical trials evaluating intratumoral DNX-2401 in adults with recurrent glioblastoma have demonstrated that the virus has a favorable safety profile and can ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07424092

NCT07424092 | Intratumoral DNX-2401 for High Grade ...

In the clinical setting, intratumoral administration of DNX-2401 has demonstrated to be safe and effective in several phase 1 and 2 clinical trials in adult ...

8.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2202028

Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic ...

Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year.