FITC-E2 CAR T Cells + Folate-Fluorescein for Osteosarcoma

Overseen By Catherine Albert, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Seattle Children's Hospital

Must not be taking: Anticancer agents

Disqualifiers: Active malignancy, Severe infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 months

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for patients with hard-to-treat or recurring osteosarcoma. It uses a special drug and modified immune cells to target and kill cancer cells. The patient's own immune cells are changed in a lab to better recognize cancer, and a drug helps these cells find and destroy the cancer.

Will I have to stop taking my current medications?

The trial requires that certain medications, like anti-cancer agents, radiotherapy, chemotherapy, and some others, be stopped within a specific 'washout' period (time without taking certain medications) before participating. It's best to discuss your current medications with the trial team to see if they need to be paused.

What data supports the effectiveness of the treatment FITC-E2 CAR T Cells + Folate-Fluorescein for Osteosarcoma?

Research shows that similar CAR T cell therapies targeting specific proteins on osteosarcoma cells, like HER2 and GD2, have been effective in reducing tumor growth and killing cancer cells in preclinical models. This suggests that using CAR T cells, like those in the FITC-E2 treatment, could potentially improve outcomes for osteosarcoma patients. ^{1 2 3 4 5}

Is the FITC-E2 CAR T Cells + Folate-Fluorescein treatment generally safe for humans?

The treatment has shown potential safety mechanisms in preclinical studies, such as the ability to manage cytokine release syndrome (CRS, a severe immune reaction) through dose adjustments and the use of sodium fluorescein. These findings suggest that the treatment can be administered with safety measures in place to mitigate severe side effects. ^{1 3 4 6 7}

How is the FITC-E2 CAR T Cells + Folate-Fluorescein treatment for osteosarcoma different from other treatments?

The FITC-E2 CAR T Cells + Folate-Fluorescein treatment is unique because it uses a switchable CAR T cell strategy, where the anti-FITC CAR T cells are activated by a specific switch molecule to target osteosarcoma tumors, allowing for controlled and targeted immune response against the cancer cells. ^{1 2 3 4 8}

Research Team

Catherine Albert, MD

Principal Investigator

Seattle Children's Hospital

Eligibility Criteria

This trial is for patients with osteosarcoma that's resistant to treatment or has returned. Participants must have a new site of disease confirmed by imaging, be able to undergo apheresis, and have a life expectancy of at least 8 weeks. They should not have HIV or hepatitis, agree to use contraception if applicable, and have good organ function. Exclusions include active severe infections, other cancers, primary immunodeficiency syndrome, pregnancy/breastfeeding, and any condition preventing protocol adherence.

Inclusion Criteria

Negative HIV, hepatitis B and C test within 3 months

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

My osteosarcoma has not responded to the first treatment and cannot be removed with surgery.

Exclusion Criteria

I have no active cancer other than my primary solid tumor.

Pregnant or breast feeding

Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and CAR T Cell Manufacturing

Blood is drawn from participants to extract T cells, which are then modified in a lab to become CAR T cells.

4-6 weeks

Treatment

Participants receive chemotherapy followed by CAR T cell infusion and escalating doses of UB-TT170.

8 months

Multiple visits for infusions and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term Follow-up

Participants who received CAR T cell infusion are monitored for long-term safety and outcomes.

15 years

Treatment Details

Interventions

• SCRI-E2CAR_EGFRtv1
• UB_TT170

Trial Overview The study tests UB-TT170 combined with modified CAR T cells against osteosarcoma. Patients' T cells are collected and engineered in the lab to target cancer flagged by UB-TT170. After chemotherapy preparation, these CAR T cells are infused back into the patient followed by regular doses of UB-TT170 to mark cancer cells for destruction by CAR T cells.

Participant Groups

Group I: UB-TT170 following SCRI-E2CAR_EGFrtv1 Experimental Treatment 2 Interventions

Following CAR T cell administration, subjects will receive a first Course of 3 escalating doses of UB-TT170 over 2 weeks followed by fixed weekly dosing for 2 weeks. If eligible, subjects may proceed to Courses 2 - 4 consisting of 7 weekly doses of UB-TT170.

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Umoja BioPharma, Inc.

Collaborator

Trials

1

Recruited

20+

Findings from Research

GD2 CAR modified T cells were found to be highly effective in killing osteosarcoma (OS) tumor cells, indicating their potential as a targeted immunotherapy for high-risk OS in children.

The study also revealed that combining GD2 CAR T cells with suboptimal doses of doxorubicin chemotherapy can enhance the cytotoxic effects against OS, suggesting a synergistic approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GD2 chimeric antigen receptor modified T cells in synergy with sub-toxic level of doxorubicin targeting osteosarcomas. Chulanetra, M., Morchang, A., Sayour, E., et al.[2020]

The engineered FR806 receptor allows for the selective targeting and elimination of T cells that have been modified for therapy, minimizing damage to normal tissues, which is crucial for safety in adoptive T cell therapies.

In experiments with immuno-compromised mice, the antibody-drug conjugate CH12-MMAF effectively eliminated most of the FR806-expressing T cells, demonstrating the efficacy of this safety switch in controlling T cell populations post-therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Fusion Receptor as a Safety Switch, Detection, and Purification Biomarker for Adoptive Transferred T Cells. Wu, X., Shi, B., Zhang, J., et al.[2018]

CAR-T cell therapy has shown high remission rates in pediatric patients with CD19+ B-cell malignancies, but challenges remain for treating solid tumors like osteosarcoma due to fewer targets and a hostile tumor environment.

The development of a CAR-T adaptor molecule (EC17 CAM) allows for targeted therapy against folate receptor-positive tumors, enhancing CAR-T cell activation and reducing the risk of severe cytokine release syndrome through careful dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of Bispecific Adaptor Molecule Controlled Folate Receptor CAR-T Cell Therapy With Special Focus on Pediatric Malignancies. Lu, YJ., Chu, H., Wheeler, LW., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Immunotherapy targeting HER2 with genetically modified T cells eliminates tumor-initiating cells in osteosarcoma. [2020]

2. England pubmed.ncbi.nlm.nih.gov

ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-modified T cells targeting EphA2 for the immunotherapy of paediatric bone tumours. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

GD2 chimeric antigen receptor modified T cells in synergy with sub-toxic level of doxorubicin targeting osteosarcomas. [2020]

5. England pubmed.ncbi.nlm.nih.gov

CAR T targets and microenvironmental barriers of osteosarcoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A Fusion Receptor as a Safety Switch, Detection, and Purification Biomarker for Adoptive Transferred T Cells. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of Bispecific Adaptor Molecule Controlled Folate Receptor CAR-T Cell Therapy With Special Focus on Pediatric Malignancies. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Switchable CAR T cell strategy against osteosarcoma. [2023]