What side effects are associated with this type of intervention?

Common treatments for Germ Cell Tumors include chemotherapy, radiation therapy, and surgery. Chemotherapy often involves drugs like cisplatin, etoposide, and bleomycin, which can cause side effects such as nausea, vomiting, hair loss, fatigue, and increased risk of infection. Radiation therapy can lead to skin irritation, fatigue, and long-term risks like secondary cancers. Surgery may result in pain, infection, and recovery-related complications. In comparison, B7H3-specific CAR T cell therapy, a form of immunotherapy, primarily involves side effects like cytokine release syndrome (fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing) and neurotoxicity (confusion, seizures, and brain swelling).

What prior FDA approvals exist?

Currently, there are no FDA-approved treatments for Germ Cell Tumors that involve genetically modified T cells or CAR T cell therapies similar to the B7H3-specific CAR T cells being studied. Traditional treatments for Germ Cell Tumors typically include surgery, chemotherapy (such as cisplatin-based regimens), and radiation therapy. Immunotherapy approaches, including CAR T cells, are being actively researched for various types of solid tumors, but specific approvals for Germ Cell Tumors have not yet been established.

What other types of research exist?

Promising novel alternatives to B7H3-specific CAR T cells for Germ Cell Tumors in 2024 include: 1) Immune checkpoint inhibitors such as pembrolizumab and nivolumab, which target PD-1/PD-L1 pathways. 2) Combination therapies involving immune checkpoint inhibitors and other agents like cetuximab. 3) Other CAR T cell therapies targeting different antigens specific to germ cell tumors. These approaches are being actively investigated and have shown potential in various solid tumors.

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CAR T-cell Therapy

CAR T Cell Therapy for Pediatric Cancer

Phase 1

Waitlist Available

Led By Navin Pinto, MD

Research Sponsored by Seattle Children's Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Evidence of refractory or recurrent disease

If no apheresis product or usable T cell product is available, at least 3 half-lives or 30 days (whichever is shorter) from time of last dose of anti-tumor directed antibody therapy (including checkpoint inhibitor) at time of enrollment

Must not have

Current relevant CNS pathology

Participant has presence of active severe infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 84 days

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment for children and young adults with hard-to-treat solid tumors. It uses the patient's own immune cells, modified to better attack cancer cells. The study aims to see if this approach is safe and effective. This type of therapy has shown remarkable results in young patients with certain types of blood cancers.

Who is the study for?

This trial is for children and young adults up to 26 years old with certain relapsed or refractory solid tumors. They must have a life expectancy of at least 8 weeks, be recovered from previous treatments, have adequate organ function and lab values, and not be pregnant or breastfeeding. Participants over 15 must agree to use effective contraception.

What is being tested?

The study tests genetically modified T cells targeting B7H3 in non-CNS solid tumors. It has two arms: one receives only B7H3-specific CAR T cells; the other also targets CD19+ B cells. The goals are to assess safety, dose tolerance, cell persistence in the body, and anti-tumor effects.

What are the potential side effects?

Potential side effects include reactions related to immune activation such as cytokine release syndrome (flu-like symptoms), toxicity due to inflammation in organs, and issues that may arise from the destruction of modified T cells by cetuximab or trastuzumab if needed.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition has not improved or has returned after treatment.

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I haven't received any antibody cancer treatment for the last 30 days or 3 half-lives, whichever is shorter.

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My cancer is not originally from the brain but has been confirmed by tissue examination.

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

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I can do most activities but need help with some.

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I am 26 years old or younger and consenting to join the study.

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I can undergo apheresis or already have an apheresis product ready for use.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a current brain or spinal cord condition.

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I am currently suffering from a severe infection.

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I have a primary immunodeficiency syndrome.

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I am currently being treated for or have symptoms of GVHD.

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I have only one type of cancer.

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I am currently undergoing external beam radiation therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 84 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~84 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 84 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express B7H3-specific CAR (Arm A)

Assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a bispecific B7H3xCD19 CAR (Arm B)

To assess the dose limiting toxicities (DLTs) and describe the full toxicity profile for each study arm

+6 more

Secondary study objectives

Describe the relative expansion and persistence of the CAR T cell product and retention of function for B7H3xCD19 bispecific CARs determined by maintenance of B cell aplasia (BCA) with and without pembrolizumab

Determine the duration of in vivo persistence of adoptively transferred T cells in the peripheral blood and compare engraftment between T cell products and treatment arms

Determine the magnitude of in vivo persistence of adoptively transferred T cells in the peripheral blood and compare engraftment between T cell products

+1 more

Other study objectives

Analyze blood, bone marrow, CSF, normal tissue, and/or tumor tissue for biomarkers of safety and/or anti-tumor activity

Assess the efficacy of infusional cetuximab and/or trastuzumab in ablating transferred T cells and ameliorating acute toxicities in treated participants

Evaluate B7H3 antigen expression in tumor tissue and/or normal tissue if a tissue biopsy, tumor biopsy, or resection is available

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: SCRI-CARB7H3(s)x19 plus pembrolizumabExperimental Treatment2 Interventions

Autologous CD4+ and CD8+ T-cells genetically modified to express a bispecific B7H3xCD19 CAR given in combination with pembrolizumab

Group II: SCRI-CARB7H3(s)x19Experimental Treatment1 Intervention

Autologous CD4+ and CD8+ T-cells genetically modified to a bispecific B7H3xCD19 CAR

Group III: SCRI-CARB7H3(s)Experimental Treatment1 Intervention

Autologous CD4+ and CD8+ T-cells genetically modified to express an B7H3-specific CAR

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Germ Cell Tumors (GCTs) include chemotherapy, surgery, and radiation therapy. Chemotherapy works by using drugs to kill rapidly dividing cancer cells, while surgery involves physically removing the tumor, and radiation therapy uses high-energy rays to destroy cancer cells. Recently, immunotherapy, such as CAR T cell therapy, has emerged as a promising treatment. CAR T cell therapy involves genetically modifying a patient's T cells to express a receptor specific to a tumor antigen, such as B7H3, enabling the T cells to target and kill cancer cells. This approach is significant for GCT patients as it offers a targeted treatment option that can potentially improve outcomes and reduce the side effects associated with traditional therapies.