A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-E2) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma

Study Overview
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Brief Summary
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The purpose of this study is to see if a new treatment could help patients who have osteosarcoma that does not go away with treatment (is refractory) or comes back after treatment (is recurrent).This study is testing a combination of study therapies, UB-TT170 and genetically modified chimeric antigen receptor T lymphocyte (CAR T) cells, which work together in a way that is different from chemotherapy. In this study, researchers will take some of your blood and remove the T cells in a process called apheresis. Then the T cells are taken to a lab and changed to CAR T cells that recognize the flags from UB-TT170. Once researchers think they have grown enough CAR T cells, called antiFL(FITC-E2) CAR T cells, to fight your cancer, you may get some chemotherapy to make room in your body for the new cells and then have those cells put back in your body. A few days after the you get your CAR T cell infusion you will start to get infusions of UB-TT170, with the dose slowly increasing for the first few infusions until you have reached a maximum dose that you will get on a regular schedule. The UB-TT170 will attach to your tumor cells and flag them so that they attract the CAR T cells. When the CAR T cells see the labeled tumor cells they can kill the tumor cells. The active part of the study lasts about 8 months, and if you get the CAR T cell infusion you will be in long-term follow-up for 15 years.

Official Title
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A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-Ew) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma

Conditions
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Osteosarcoma

Intervention / Treatment
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* Biological: SCRI-E2CAR_EGFRtv1
* Drug: UB_TT170


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory or recurrent/progressive osteosarcoma that has failed first line therapy for Osteosarcoma per NCCN or upfront Children's Oncology Group clinical trial and is not amenable to surgical resection (must meet one of the following): New site of measurable disease by radiographic imaging or histologic confirmation New site of evaluable disease by radiographic imaging (including FDG-PET) or histologic confirmation Greater than 20% increase in at least one tumor dimension documented by CT/MRI, AND a maximum absolute increase of 5 mm in longest dimension of existing lesion(s) (previously irradiated lesions may be included) Persistent measurable disease or FDG-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy and/or chemotherapy) Able to tolerate apheresis, including placement of temporary apheresis catheter, if necessary, or already has an apheresis product available for use in manufacturing Life expectancy ≥ 8 weeks Lansky or Karnofsky score ≥ 50 Anti-cancer agents, radiotherapy, cytoxic chemotherapy, biologic therapy, anti-tumor antibody therapy, genetically modified cell therapy, and, if no apheresis product available, corticosteroid therapy (excluding physiologic replacement), discontinued within protocol specified wash-out period Adequate hematologic, renal, hepatic, cardiac, and respiratory function. Negative HIV, hepatitis B and C test within 3 months If of child-bearing or fathering potential, willing to use highly effective contraception through 12 months following final stud drug infusion Exclusion Criteria: Active malignancy other than primary malignant solid tumor diagnosis (CNS intracranial metastases are allowed) Ongoing, symptomatic CNS pathology requiring medical intervention Receiving external beam radiotherapy Presence of active, severe infection Primary immunodeficiency syndrome Pregnant or breast feeding Unwilling to provide consent/assent for study participation, including 15 year follow up Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UB-TT170 following SCRI-E2CAR_EGFrtv1<br>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. | Biological: SCRI-E2CAR_EGFRtv1<br>* Autologous CD4+ and CD8+ T cells that have been genetically modified to express antiFL(FITC-E2)<br>Drug: UB_TT170<br>* Bispecific small molecule adapter formulated with phosphate buffered saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events associated with ex-vivo expanded autologous T cells genetically modified to express an antiFL(FITC-E2) CAR administered with UB-TT170 will be assessed | The type, frequency, severity, and duration of adverse events will be summarized | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability to manufacture antiFL(FITC-E2) CAR cells | The number of successfully manufactured antiFL(FITC-E2) CAR products will be assessed | 28 Days | 
| Evaluate the pharmacokinetics of UB-TT170 in combination with the anti-FL(FITC-E2) CAR T cells | Pharmacokinetics of UB-TT170 in combination with the anti-FL(FITC-E2) CAR T cells | 25 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteosarcoma, bone cancer, pediatric sarcoma, young adult sarcoma