Autologous B7-H3 Chimeric Antigen Receptor T Cells in Relapsed/Refractory Solid Tumors

NCT06500819 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: IRB-74070NCI-2025-00267
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the manufacturing feasibility and safety of intravenous (IV) administration of B7-H3CART in children and young adult subjects with relapsed and/or refractory solid tumors expressing B7-H3 target using a standard 3+3 dose escalation design.

Conditions

Neuroblastoma; Sarcoma; Osteosarcoma

Keywords

Chimeric Antigen Receptor; Autologous T-Cells

Outcome Measures

Primary Outcomes (2)

• Feasibility of manufacturing autologous T cells

  Feasibility of manufacturing autologous T cells transduced with Ef1a-CAR276 lentiviral vector expressing B7-H3 Chimeric Antigen Receptor (B7-H3-CART), using the Miltenyi CliniMACS Prodigy® system with dasatinib and protamine sulfate.

  2 years

• Safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of a single dose of intravenous B7-H3CART

  Assess the safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of a single dose of intravenous B7-H3CART in children and young adults with relapsed and refractory solid tumors (i.e. soft tissue sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma) using the proposed dose escalation schedule.

  2 years

Secondary Outcomes (2)

• Clinical response in children and young adults

  2 years

• Safety of B7-H3CART at the MTD/RP2D

  2 years

Study Arms (1)

Lymphodepletion

EXPERIMENTAL

Fludarabine 30 mg/m2 per day IV for 4 days: 5, -4, 3, -2 Cyclophosphamide 500 mg/m2 per day IV for 3 days: -5, -4, -3 Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0.

Drug: B7-H3CART Dose (Intravenous)

Interventions

B7-H3CART Dose (Intravenous) DRUG

Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level -1 (DL-1) 0.3 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 1 (DL1) 1 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 2 (DL2) 3 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 2 (DL2) 3 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 3 (DL3) 9 x 106 transduced T cells/kg

Lymphodepletion

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Histologically confirmed malignant solid tumor (including neuroblastoma, soft tissue sarcoma, osteosarcoma, Ewing Sarcoma, and Wilms tumor) with evidence of incurable disease and tumor recurrence/progression after all available curative standard therapies.
• Subjects with neuroblastoma must have received or be intolerant to anti-GD2 antibody therapy.
• Subjects with Wilm's tumor must have received or be intolerant to ifosfamide or cyclophosphamide plus etoposide therapy or alternative salvage regimen.
• Subjects with embryonal rhabdomyosarcoma must have received or be intolerant to Adriamycin-based therapy.
• Subjects with surgically resected pulmonary osteosarcoma in first recurrence must have received surgical resection of metastatic nodules.
• Subjects during dose escalation must have evaluable or measurable disease. Subjects during dose expansion must have measurable disease, except neuroblastoma which may have MIBG positive disease only.
• B7-H3 positive expression on malignant cells is NOT required but archival tissue must be available, or the subject must be willing to undergo tissue biopsy for expression analysis.
• Age: Must be ≥ 2 and ≤ 30 years of age.
• \* For the first three subjects treated with B7-H3CART, must be ≥ 12 and ≤ 30 years of age.
• Performance Status: Patients \> 16 years of age must have Karnofsky ≥ 50%. Patients ≤ 16 years of age must have Lansky scale ≥ 50%; or ECOG performance status ≤ 2.
• Prior Therapy
• No limit to the number of prior therapies.
• Prior Therapy Wash-out: At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives. Radiation therapy must have been completed at least 3 weeks prior to enrollment, with the exception that there is no time restriction if the subject has measurable/evaluable disease outside the radiation port or the site of radiation has documented progression.
• Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)
• ANC ≥ 750/uL\*

You may not qualify if:

• Receiving any other current investigational agents.
• History of other malignancy, except non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast), unless disease free for at least 3 years.
• Presence of untreated brain metastases will be excluded. Subjects with previous CNS tumor involvement that has been treated and is stable for at least 3 months following completion of therapy are permitted. Patients who are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits, and no progression of residual brain abnormalities without specific therapy, are permitted.
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti HCV positive) as the immunosuppression contained in this study will pose unacceptable risk. A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• Any medical condition that in the judgement of the sponsor investigator is likely to interfere with assessment of safety or efficacy of study treatment.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Pregnant females are excluded from this study because the effects of autologous B7-H3CART on the developing human fetus are unknown and because the chemotherapy agents used in this trial (cyclophosphamide and fludarabine) are category D agents with the potential for teratogenic or abortifacient effects. Additionally, because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with cyclophosphamide/fludarabine, breastfeeding should be discontinued if the mother is treated with cyclophosphamide/fludarabine. These potential risks may also apply to other agents used in this study.
• Primary immunodeficiency or history of systemic autoimmune disease (e.g., Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
• Patients who require systemic corticosteroid or other immunosuppressive therapy. (A one-week washout from systemic corticosteroid or other immunosuppressive therapy is permitted.) Use of physiologic doses of corticosteroids (up to 3 mg/m2/day prednisone equivalent) are permitted. Use of topical, ocular, intra-articular, intra-nasal, or inhaled corticosteroids are permitted.
• In the investigator's judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Sarcoma; Osteosarcoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Study Officials

• Sneha Ramakrishna, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Li

CONTACT

650-497-8953; solidtumorcart@stanfordchildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 15, 2024
• Study Start: July 11, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: May 7, 2026

Record last verified: 2026-05

Locations

US (1)