Dose Ranging, Toxicity Seeking, Phase 1 Trial of Oncolytic Adenoviral Therapy for Melanoma Intracranial and Extracranial Metastases

NCT07444606 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-2037NCI-2026-01461
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the recommended dose level and recommended number of injections of the study agent DNX-2401 that can be given to patients with metastatic melanoma that have intracranial and/or extracranial lesions.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (3)

GroupA-Arm1: IC virus delivery followed by surgical resection

EXPERIMENTAL

Participants will receive 1 injection of DNX-2401.

Drug: DNX-2401

Group A-Arm 2: DL1, DL2, DL3

EXPERIMENTAL

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.

Drug: DNX-2401

Group B: Patients with either EC or EC and IC disease

EXPERIMENTAL

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

Drug: DNX-2401

Interventions

DNX-2401 DRUG

Given by injection

Group A-Arm 2: DL1, DL2, DL3; Group B: Patients with either EC or EC and IC disease; GroupA-Arm1: IC virus delivery followed by surgical resection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (For both Groups):
• \. Patients must be 18 years old or older. 2. Patients must have a diagnosis of stage IV melanoma. 3.Patients must have an ECOG Performance status of 0 or 1 (may be obtained from medical records within 24 days of screening if not performed at screening).
• Patients must be able to complete an MRI of the head with contrast. 5.For women of childbearing potential only, a negative urine or serum pregnancy test is required at screening. Women must agree to notify investigator immediately if they become pregnant at any time during the trial period.
• Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 6 months from administration of virus. Birth control that is acceptable to use in this study:
• Using twice the normal protection of birth control (i.e., double barrier) by using a condom AND spermicidal jelly or foam, or a diaphragm AND spermicidal jelly or foam. A spermicidal jelly or foam must be used in addition to a barrier method (e.g., condom or diaphragm)
• Birth control pills ("The Pill")
• Depot or injectable birth control
• IUD (Intrauterine Device)
• Birth Control Patch (e.g., Othro Evra®)
• NuvaRing®
• Surgical sterilization (i.e., tubal ligation or hysterectomy for women or vasectomy for men)
• Patients must be able and willing to provide informed consent. A legally authorized representative (LAR) may provide consent if the potential subject lacks the capacity to provide consent themselves. Patient assent will be sought where feasible in this situation.
• For patients enrolled in Groups A and B, patients must be relapsed or refractory to standard of care therapy. Additionally, patients must continue with immunotherapy while undergoing oncolytic viral treatment at the discretion of the medical oncologist. 9. Patients enrolled in Group A or Group B must be on one of the following FDA approved immunotherapy agents: Ipilimumab, Nivolumab, Pembrolizumab, Relatlimab.
• \. Normal hematologic, renal and liver function as defined by:
• \- ANC ≥1000/ mm3

You may not qualify if:

• (For Both Groups):
• Patients with \>5 diagnosed intracranial metastases on screening MRI
• Patients who received prior WBRT or SRT for brain metastases within 2 days of study treatment initiation
• Patients with symptomatic intracranial metastases
• Patients who received high dose corticosteroids defined as dexamethasone greater than 2mg per day within 7 days of initiating therapy. However, if they have been on a stable dose of 2 mg or less per day for 7 days they can be enrolled.
• Patients with suspected or confirmed leptomeningeal disease defined as radiographic evidence by MRI of leptomeningeal involvement in addition to positive cerebrospinal fluid (CSF) cytology
• Serum lactate dehydrogenase ≥1.5x upper limit of normal
• Primary uveal or mucosal melanoma
• Patients who are checkpoint inhibitor naïve.
• Active uncontrolled infection or unstable or severe intercurrent medical conditions which would impact the ability to participate in the study. All patients must be afebrile at baseline and not taking antiviral or oral antibiotics.
• \. Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery. If the medication can be discontinued, based on the clinical judgment of the surgeon, prior to oncolytic viral administration, the patient may be eligible.
• \. Known infections with hepatitis B (positive HBsAg), hepatitis C (positive hepatitis C RNA), or HIV
• \. Patients with known or suspected immunosuppressive disorders, such as acquired or congenital/immune deficiency syndromes and autoimmune diseases
• \. Tumor position that, in the Investigator's opinion, would require ventricular, brainstem or posterior fossa injection in order to deliver the virus
• \. Any contraindication for undergoing MRI such as: individuals with pacemakers, epicardial pacer wires, infusion pumps, surgical and/or aneurysm clips, shrapnel, metal prosthesis, implants with potential magnetic properties, metallic bodies in the eyes, etc.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Christopher Alvarez-Breckenridge, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christopher Alvarez-Breckenridge, MD, PHD

CONTACT

(713) 792-2400; calvarez11@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 3, 2026
• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

US (1)