FDA authorizes direct CSF injection of DNG64-CAR-V for second brain cancer patient

FDA CBER authorized emergency use of intraventricular DNG64-CAR-V for a second patient with diffuse midline glioma and leptomeningeal disease in Los Angeles. The move could open a new delivery route for tumor-targeted gene therapy in cancers that spread to the brain and spinal cord.

Why it matters: - FDA CBER authorization opens a direct-to-cerebrospinal-fluid delivery path for DNG64-CAR-V in a patient with leptomeningeal disease. - The approach is aimed at advanced central nervous system cancers and cancers that spread to the brain and spinal cord, a setting with few treatment options. - The authorization could support broader access if the planned Phase I/II leptomeningeal disease trial moves forward.

What happened: - The Cancer Center of Southern California/Sarcoma Oncology Center and the Aveni Foundation announced FDA CBER emergency use authorization for intraventricular injection of DNG64-CAR-V. - The authorization applies to a second patient with diffuse midline glioma and leptomeningeal disease under IND #33293. - The request covered “Right to Try” intraventricular injection of DNG64-CAR-V and placement of an Ommaya reservoir for direct administration into cerebrospinal fluid. - The announcement was made Sept. 23, 2026, from Los Angeles.

The details: - The treatment is given weekly for about four months. - CSF samples are withdrawn from the Ommaya reservoir before and after each injection to assess response. - DNG64-CAR-V, also called DeltaRex-G, is described as a tumor-targeted gene delivery system created by Drs. Erlinda M. Gordon and Frederick L. Hall at the USC Keck School of Medicine. - The therapy can be administered intravenously, intratumorally, intra-arterially and intrathecally. - The product is described as an off-the-shelf, injectable, replication-incompetent amphotropic retroviral vector encoding a Cyclin G1/CCNG1 inhibitor construct. - The company says the therapy kills cancer cells, tumor blood supply and cancer-associated fibroblasts in the tumor microenvironment. - The therapy is also described as reducing stroma and improving entry of chemoimmunotherapy drugs into the tumor microenvironment. - Intravenous DNG64-CAR-V has been used in phase I/II studies for sarcoma, pancreatic cancer and breast cancer, and in a phase II trial for osteosarcoma that had failed standard chemotherapy. - The release cites reports of long-term survivors and no delayed adverse events in those studies, including a 10- to 18-year survival range. - DNG64-CAR-V is available through an expanded access program sponsored by the Aveni Foundation under NCT04091295.

Between the lines: - The authorization signals that FDA CBER is willing to consider individualized, route-specific use of the therapy for severe CNS disease. - The direct CSF approach is designed to reach disease sites that may be difficult to treat with standard systemic delivery. - The release positions leptomeningeal disease as the next likely focus area for formal study, which suggests the expanded-access case may feed into a broader clinical development plan.

What's next: - Dr. Chawla said a Phase I/II clinical trial for leptomeningeal disease is planned. - Additional patients with leptomeningeal disease have already requested consideration for the treatment, according to the release. - The Aveni Foundation says the therapy remains available through its expanded access program.

The bottom line: - FDA authorization gives DNG64-CAR-V a new delivery route for a patient with leptomeningeal disease and could help set up the next stage of testing in hard-to-treat brain and spinal cord cancers.