A Phase 0/1 Study of cDNA for TP53, Checkpoint Inhibition and Radiation in Children With Recurrent, Progressive or Refractory CNS Malignancies.

Summary

This clinical trial is studying a drug called SGT-53 along with radiation and another drug called Nivolumab. It's for children with brain tumors that have come back, gotten worse, or didn't get better with earlier treatments. The main questions it aims to answer are:

What is the right dose of SGT-53 that children can safely receive when it is used with radiation and Nivolumab? This dose will be used in the second phase of the trial.

What side effects are there of SGT-53 when it is used with radiation and Nivolumab?

How does SGT-53 move through the body when given with radiation and Nivolumab?

How much of the SGT-53 drug is found in the tumor tissue? This will be tested in a small group of patients?

Participants will:

For the first treatment cycle:

Get SGT-53 twice per week Get Nivolumab every 2 weeks Receive radiation therapy during week 2

For Cycles 2-6:

Get SGT-53 once per week during even cycles and twice per week during odd cycles Get Nivolumab every 2 weeks For Cycles 7+ Get both SGT-53 and Nivolumab every 2 weeks In the phase 0 part of the study, 4 participants will have genetic testing performed on their tumor tissue after receiving SGT-53. These samples will be compared to another sample taken from the skin.

Conditions

• CNS Malignancies
• Medulloblastoma Recurrent
• ATRT Recurrent
• Pineoblastoma
• Embryonal Neoplasm
• Ependymoma Recurrent
• High Grade Gliomas

Interventions

DRUG

SGT-53

SGT-53 is a novel cationic liposome encapsulating a normal human wild type TP53 cDNA sequence in a plasmid backbone. The liposome is decorated on its surface with an anti- transferrin receptor (TfR) single chain antibody fragment (scFv) that is designed to target cancer cells through the binding of the TfRscFv to the transferrin receptor. This complex has been shown to efficiently and specifically deliver the TP53 complementary DNA (cDNA) to the tumor cells via receptor-mediated endocytosis of the cationic liposomal complex. Introduction of the TP53 cDNA sequence restores wild-type p53 (wtp53) function in the apoptotic pathway.

RADIATION

hypofractionated radiotherapy with immunotherapy

Re-irradiation has rapidly grown into a primary consideration in the context of recurrent pediatric CNS malignancies. While not thought to be curative by itself, it has often resulted in temporary symptomatic improvement as well as occasional radiographic regression or stabilization, although as with any irradiation, may also cause some adverse events.

DRUG

Nivolumab

Given the poor prognosis for children with recurrent CNS malignancies and the importance of p53 function in these tumors, we propose a pilot study of SGT-53 in combination with re-irradiation and checkpoint inhibition followed by maintenance therapy with SGT-53 in combination with nivolumab to evaluate the safety, feasibility and preliminary efficacy. SGT-53 will be added to a salvage regimen utilized in patients with recurrent tumors of re- irradiation and nivolumab followed by combination therapy with SGT-53 and nivolumab.

Sponsors & Collaborators

• Children's National Research Institute

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

3 Years

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-12-16

Primary Completion

2028-05-01

Completion

2028-05-01

FDA Drug

Yes

Countries

• United States

Study Locations