The purpose of this study is to assess the safety, feasibility, and effectiveness of a consolidative B7-H3 CAR T cell therapy in patients with newly diagnosed high-risk osteosarcoma who have undergone upfront standard chemotherapy.
Primary Objectives:
\- To evaluate 1-year RFS from the time of SJCARB7H3-41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy.
Secondary Objectives:
* To evaluate the OS from time of SJCARB7H3-41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy. * To evaluate the feasibility of delivering SJCARB7H3-41BBL at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma. * To describe the safety of autologous SJCARB7H3-41BBL therapy when delivered at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma.
Participant and/or legally authorized representative has signed the Informed Consent Form for this study
Regimen A only: Completed all planned cycles of consolidation therapy between 14-28 days prior.
Regimen B only: has completed all planned cycles of consolidation chemotherapy at least 14 days prior and if clinically indicated, participant has undergone pulmonary metastasectomy. They must have recovered from any surgical complications with no ongoing sequelae of category 2 or higher by the Clavien-Dindo classification system and less than 6 weeks must have passed from time of pulmonary metastasectomy.
No evidence of progressive disease since enrolled on study
Major surgical adverse event related to the primary tumor local control defined as Clavien-Dindo category 3 requiring ongoing wound care.
Evidence of clinically significant encephalopathy/new focal neurologic deficits.
positive blood culture within 48 hours of enrollment, OR
fever above 38.2° C, AND clinical signs of infection within 48 hours of enrollment
Single group
Cyclophosphamide
DrugIV
Fludarabine
DrugIV
Mesna
DrugIV prior to and again at 3, 6, and 9 hours following each dose of cyclophosphamide.
Apheresis
Procedure/SurgeryIV collection
SJCARB7H3_41BBL infusion
Procedure/Surgery1X107 CAR+ T cells/kg
Event-free survival (EFS), defined as time from SJCARB7H3-41BBL infusion to disease relapse, progressive disease, new systemic therapy, secondary malignancy or death
Event-free participants will be censored at the time of last follow-up. This analysis will report the Kaplan-Meier (KM) curve, along with the 12-month EFS estimate and its 80% confidence interval using the arcsine-square root transformation. Evaluable participants are those who complete standard chemotherapy, receive SJCARB7H3-41BBL and are treated on the regimen used for the Efficacy phase.
Overall survival (OS), defined as time from SJCARB7H3-41BBL cell infusion to all-cause mortality.
Event-free participants will be censored at the time of last follow-up. OS will be reported similarly to the EFS endpoint on the same participant subset.
Number of participants experiencing protocol-specified regimen-related toxicities.
This outcome measure will be descriptively summarized for the overall participant group and by regimen (if more than 1 regimen is evaluated) for each regimen-related toxicity. Evaluable participants include those who receive SJCARB7H3\_41BBL and remain on protocol therapy through at least 28 days post-infusion or experience a related unacceptable toxicity.
Number of participants with successful manufacture of SJCARB7H3-41BBL cells of sufficient dose and planned product administration
This outcome measure will be descriptively summarized for the overall participant group and by regimen (if more than 1 regimen is evaluated) for participants who undergo apheresis and remain on protocol therapy through the end of standard therapy.
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