B7-H3.CD28Z.CART in Solid Tumors

NCT07358260 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-648
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research study is to test if a new cell therapy (B7-H3.CD28Z.CART / B7-H3 CAR T cells) is safe and effective in treating children and young adults with solid cancers whose tumors have returned or stopped responding to standard treatments (relapsed or refractory) and have been identified with a B7-H3 marker. The names of the treatment interventions used in this study are:

• B7-H3.CD28Z.CART / B7-H3 CAR T cells
• Fludarabine
• Cyclophosphamide

Conditions

Pediatric Solid Tumor; Neuroblastoma

Keywords

Relapsed Solid Tumor; Refractory Solid Tumor; Pediatric Solid Tumor; Neuroblastoma

Outcome Measures

Primary Outcomes (2)

• Manufacturing Success Rate of Autologous B7-H3.CD28Z CART Cells

  Each participant's product will be tested for the following criteria: cell viability ≥ 70%; cell number within ± 20% of the planned dose; CD3+ T cells ≥ 80% of leukocytes; CAR-positive cells ≥ 10% of CD3+ T cells; endotoxin ≤ 5 EU/kg; mycoplasma not detected; vector copy number (VCN) per transduced cell ≤ 10; replication-competent retrovirus (RCR) not detected; and sterility confirmed as "No Growth to Date" (NGTD) after a minimum of 5 days in culture. A participant will be classified as a manufacturing success if the final product satisfies all release criteria. If any criterion is not met, the participant will be classified as a manufacturing failure. The manufacturing success rate is defined as the proportion of participants classified as a success.

  Participants will receive the CART cell infusion on Day 0.

• Maximum Tolerated Dose (MTD) of B7-H3.CD28Z.CART Cells

  The MTD is defined as the highest dose level of B7-H3.CD28Z.CART cells at which the rate of dose-limiting toxicity (DLT) is acceptable per the modified 3+3 design. The recommended phase 2 dose (RP2D) is the MTD of single-agent autologous B7-H3.CD28Z.CART cells. Additional details are provided in Protocol Section 13.1.

  28 days

Secondary Outcomes (7)

• Number of Participants Experience Dose-Limiting Toxicity (DLT)

  28 days

• Adverse Events of Special Interest (AESI) Rate on the First Infusion

  15 years

• Objective Response Rate (ORR)

  Disease assessments will be performed at Day 28, month 3, and then every 3 months through month 24 or up to month 48, if received second infusion.

• Median Progression-Free Survival (PFS)

  Disease assessments will be performed at Day 28, month 3, and then every 3 months through month 24 or up to month 48, if received second infusion.

• Median Overall Survival (OS)

  15 years

Study Arms (1)

DOSE ESCALATION B7-H3.CD28Z.CART CELL Therapy

EXPERIMENTAL

3+3 dose-escalation to define maximum tolerated dose (MTD) and Phase 2 Recommended Dose (RP2D) of autologous B7-H3.CD28Z.CART cells, followed by 2 expansion cohorts (neuroblastoma; other B7-H3-positive solid tumors) at RP2D. * Screening/Baseline: Consent, eligibility, history, exam, performance status, labs (incl. HIV, hepatitis, pregnancy), ECG, echocardiogram (as indicated), imaging and/or bone marrow, neurologic exam. * Leukapheresis: Autologous T-cell collection for CAR T manufacturing prior to lymphodepletion. * Lymphodepleting chemotherapy (Days -4 to -2): Fludarabine + cyclophosphamide IV. * Day 0: Single IV B7-H3.CD28Z.CART infusion (inpatient), with ≥7 days post-infusion monitoring. * Follow-up: Safety and disease assessments through 24 months, then annual long-term gene-therapy follow-up to 15 years. * Optional second infusion: Allowed ≥60 days and ≤2 years after first, with repeat lymphodepletion and same follow-up.

Biological: B7-H3.CD28Z.CART; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

B7-H3.CD28Z.CART BIOLOGICAL

Modified autologous T cells administered via Intravenous (IV) infusion

DOSE ESCALATION B7-H3.CD28Z.CART CELL Therapy

Fludarabine DRUG

Administered intravenously

Also known as: Fludara

DOSE ESCALATION B7-H3.CD28Z.CART CELL Therapy

Cyclophosphamide DRUG

Administered intravenously

Also known as: Cytoxan, Frindovyx, Neosar

DOSE ESCALATION B7-H3.CD28Z.CART CELL Therapy

Eligibility Criteria

• Age: 9 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Eligibility Criteria for Prescreening
• Purpose of prescreening is to establish B7-H3 expression by IHC performed at Boston Children's Hospital. This can be performed at any time prior to completing the protocol screening process. Participants who meet the following criteria, will be offered participation in the full screening process and protocol enrollment, if eligible:
• Participants must have histologically confirmed diagnosis of a solid tumor that is relapsed or refractory for which standard curative measures do not exist or are no longer effective.
• Participant must have adequate pre-trial tumor material available to determine B7-H3 status. Tumor tissue from the most recent resection or biopsy of recurrent disease is preferred. If unavailable, tumor tissue from prior recurrences or from the time of initial diagnosis is acceptable.
• Age \>=9 months and \<30 years.
• Lansky/Karnofsky performance status ≥50% (see Appendix A)
• Life expectancy of greater than 12 weeks
• Participants who are screened for this trial should be reasonably anticipated to meet the eligibility criteria for enrollment described in Section 3.2 if their tumor is B7-H3-positive.
• Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document for prescreening.
• Eligibility Criteria for Enrollment The following criteria are required for initial study enrollment. Once enrolled, participants will need to meet specific criteria prior to lymphocyte apheresis, prior to the receipt of lymphodepletion chemotherapy and B7-H3.CD28Z.CART cell infusion as outlined in the Treatment Section of the Protocol.
• Laboratory tests required for eligibility must be completed within 28 days prior to the date of registration. Disease evaluation is required only if needed for eligibility.
• The screening window is 28 days.
• Participants must have histologically confirmed diagnosis of a solid tumor that is relapsed or refractory for which standard curative measures do not exist or are no longer effective.
• Participants must have measurable or evaluable disease for dose escalation. For expansion phase, participants with neuroblastoma must have measurable or evaluable disease by INRC. Participants with other solid tumors must have measurable disease by RECIST1.1 for the expansion phase.
• B7-H3 expression: Demonstration of B7-H3 expression with H score \>100 by immunohistochemistry (IHC) is required by IHC performed at Boston Children's Hospital. Participants may choose to enroll on the prescreening portion, which allows for assessment of B7-H3 expression only, prior to enrollment on the full clinical trial as described in Section 3.1.

You may not qualify if:

• Participants who are receiving any other investigational agents.
• Participants with known current brain metastases or leptomeningeal disease. Prior CNS metastatic disease is allowable if prior resection and/or radiation occurred at least 8 weeks prior to enrollment, without any intervening CNS metastasis, progression or recurrence, and participants are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits, and no progression of residual brain abnormalities.
• Participants with any prior immunodeficiency or history of autoimmune disease requiring systemic steroids/ immunosuppressive medication/ disease modifying agents within the last 2 years
• Prior solid organ transplant. Prior allogeneic or autologous stem cell transplant is permitted as outlined in Section 3.2.
• Active or uncontrolled viral, bacterial or fungal infection. Participants may be receiving ongoing therapy for controlled infection.
• Participants with a known additional malignancy other than non-melanomatous skin cancer or carcinoma in situ, unless not requiring active treatment and stable or disease-free for at least 3 years.
• CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that in the judgement of the investigator may impair the ability to evaluate neurotoxicity.
• History of severe hypersensitivity reaction to compounds of similar chemical or biologic compositions to any agents used in the study or in the manufacturing of cells.
• HIV/HBV/HCV infection: Participants are required to be negative for HIV Antibody or HIV viral load, negative for Hepatitis surface antigen (HbsAg) or viral load and negative for HCV antibody or HCV viral load. These participants are ineligible because of the potential for in vivo retroviral recombination events that could lead to replication-competent γ-retrovirus. A history of HIV, Hepatitis B, or Hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because the effects of B7-H3.CD28Z.CART cells on the developing fetus are unknown and because chemotherapeutic agents with the potential for teratogenic or abortifacient effects are used in this study. Because there is an unknown but potential risk for adverse events in nursing infants, secondary to treatment of the mother with B7-H3.CD28Z.CART cells and chemotherapy, breastfeeding should be discontinued if the mother is treated with T cells on this study (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).

Sponsors & Collaborators

• Robbie Majzner: lead
• Band of Parents: collaborator

Study Sites (1)

Dana Farber Cancer Institite

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Natalie Collins, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Collins, MD

CONTACT

617-632-3027; nbcollins@partners.org

Study Design

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

Study Record Dates

• First Submitted: January 14, 2026
• First Posted: January 22, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)