SGT-53 + Nivolumab + Radiation for Brain Tumors

(JACOB Trial)

Overseen By Julia Batarseh

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Children's National Research Institute

Must not be taking: Investigational drugs, Live vaccines

Disqualifiers: Low-grade glioma, Diffuse midline gliomas, Autoimmune diseases, HIV/AIDS, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for children whose brain tumors have returned or worsened after other treatments. It aims to find the safest dose of SGT-53 (an experimental treatment) when used with radiation and Nivolumab (an immunotherapy), and to understand its side effects and how it moves through the body. The trial seeks children with brain tumors like medulloblastoma or high-grade gliomas that haven't responded to prior treatments. Participants should have already tried standard treatments and still have tumors that are growing. As an Early Phase 1 trial, this research focuses on understanding how this new treatment works in children, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop chemotherapy at least two weeks before starting the study treatment and biological therapy at least one week before. If you're on corticosteroids, you need to be on a stable or decreasing dose for at least one week before enrolling. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SGT-53 has undergone testing in several studies to assess its safety. In one study, SGT-53 was combined with another drug and was generally well-tolerated by patients with advanced cancer. Some participants experienced side effects, mostly mild to moderate. Another study examined SGT-53 with radiation in children, suggesting early signs of safety, though more data is needed for certainty.

Nivolumab is more familiar and has been used to treat various conditions, including some brain tumors. Research indicates it can reach brain tumors and assist the immune system in fighting cancer. The side effects of Nivolumab are generally known and similar to those in patients with other cancers. Most side effects can be managed, but some may be more serious.

Overall, both SGT-53 and Nivolumab have shown signs of safety in earlier studies, but this trial is crucial to understand how they work together. Participants should consult their healthcare providers about any concerns to make informed decisions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SGT-53 combined with Nivolumab for brain tumors because these treatments offer a fresh approach to tackling this challenging condition. Unlike traditional therapies like surgery, chemotherapy, or radiation alone, SGT-53 uses a unique delivery system to directly introduce a tumor-suppressing gene into cancer cells, potentially enhancing the effectiveness of the treatment. When paired with Nivolumab, an immunotherapy drug that helps stimulate the body's immune system to attack cancer cells, this combination could provide a more targeted and potent response against tumor growth. The integration of these innovative mechanisms holds promise for improving outcomes in patients with hard-to-treat brain tumors.

What evidence suggests that this trial's treatments could be effective for brain tumors?

Research has shown that SGT-53, a treatment delivering the p53 gene directly to tumors, can enhance the body's immune response against cancer. It has shown promise in making brain tumors more responsive to treatments that block the PD-1 protein, which helps tumors evade the immune system. In this trial, participants will receive SGT-53 alongside Nivolumab and radiation. Nivolumab has effectively reached brain tumors and boosted immune responses. Studies have demonstrated that it can enhance T-cell responses, which are crucial in defending against cancer cells. Together, these treatments aim to improve the immune system's ability to attack brain tumors. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for children with certain types of brain tumors that have returned or didn't respond to previous treatments. Participants must be between 3 and 22 years old, have had radiation as part of initial therapy, and received at least one standard treatment. They should be recovered from prior therapies and surgeries, with a body surface area (BSA) of at least 0.6m2.

Inclusion Criteria

I have recovered from the side effects of my previous treatments.

I received my last biological treatment more than 7 days ago.

My brain tumor is growing or returning and cannot be cured with known treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0 Treatment

Participants receive SGT-53 twice per week, Nivolumab every 2 weeks, and radiation therapy during week 2. Genetic testing is performed on tumor tissue.

4 weeks

Multiple visits for treatment and testing

Phase 1 Treatment Cycles 2-6

Participants receive SGT-53 once per week during even cycles and twice per week during odd cycles, and Nivolumab every 2 weeks.

10 weeks

Bi-weekly visits for treatment

Phase 1 Treatment Cycles 7+

Participants receive both SGT-53 and Nivolumab every 2 weeks.

Ongoing

Bi-weekly visits for treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated Radiotherapy
• Nivolumab
• SGT-53

Trial Overview The study tests SGT-53 in combination with Nivolumab and hypofractionated radiotherapy on pediatric patients. It seeks the safe dose level of SGT-53 for future phases, examines side effects, studies how SGT-53 distributes in the body, and measures its concentration in tumor tissue.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 3 Interventions

Patients with recurrent, progressive, or refractory CNS malignancies receiving SGT-53, Nivolumab, and radiation.

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37146754/

Systemic and Intracranial Outcomes With First-Line ... In patients with baseline brain metastases, 5-year systemic and intracranial progression-free survival rates were higher with nivolumab plus ...

2. jto.org jto.org/article/S1556-0864(23)00525-7/fulltext

Systemic and Intracranial Outcomes With First-Line ... In patients with baseline brain metastases, 5-year systemic and intracranial progression-free survival rates were higher with nivolumab plus ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e14001

Real-world outcomes in patients with brain metastases ... Thirty-nine patients had brain metastasis at the time of nivo-rela initiation. Most patients (30 of 44 [68.2%]) had 1-3 MBM, while (14 of 44 [ ...

4. academic.oup.com academic.oup.com/neuro-oncology/article/25/8/1530/7048451

Nivolumab with or without ipilimumab in pediatric patients with ... Nivolumab (NIVO) and NIVO + ipilimumab (IPI) did not improve survival in patients with newly diagnosed diffuse intrinsic pontine glioma ...

5. aacrjournals.org aacrjournals.org/cancerimmunolres/article/12/9/1202/747081/Nivolumab-Reaches-Brain-Lesions-in-Patients-with

Nivolumab Reaches Brain Lesions in Patients with Recurrent ... Our study demonstrates that nivolumab does reach the GBM tumor lesion and enhances antitumor T-cell responses both intratumorally and systemically. However, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9298991/

Safety and efficacy of nivolumab plus ipilimumab in patients ... The median progression‐free survival was 9.0 months (95% CI, 2.9‐12.0 months), and the median overall survival was not reached (95% CI, 14.1 months to not ...