GD2IL18CART Combined With Bevacizumab for Relapsed and Refractory GD2-positive Solid Tumors

This study will test a chimeric antigen receptor (CAR) T-cell treatment combined with bevacizumab in children and young adults with relapsed or refractory neuroblastoma, Ewing sarcoma, or osteosarcoma. The CAR T-cell treatment, called GD2IL18CART, is made from a patient's own T cells. The T cells are genetically modified to recognize GD2, a molecule found on the surface of these cancers, and to release the immune-stimulating protein interleukin-18 (IL-18) when they encounter tumor cells. Bevacizumab is an antibody that blocks vascular endothelial growth factor (VEGF), a protein that affects tumor blood vessels and may make it difficult for immune cells to enter tumors. Combining bevacizumab with GD2IL18CART may therefore help more CAR T cells reach the tumor and improve their antitumor activity. The main goals of this study are to determine whether the combination can be given safely, identify a recommended dose of GD2IL18CART for use with bevacizumab, and look for early evidence of antitumor activity. The study will also examine blood and tumor samples to better understand how the treatment affects CAR T cells and the tumor environment.

Inclusion Criteria: * Participants must have relapsed and/or refractory neuroblastoma, osteosarcoma, or Ewing sarcoma judged to be incurable with conventional treatment and meet the following disease-specific requirements: * Neuroblastoma: Patients with locoregional recurrence must have received surgery and/or radiotherapy followed by relapse chemotherapy. Patients with metastatic recurrence after initial classification as intermediate risk must have received high-risk therapy. Patients with recurrence after initial classification as high risk must have received relapse chemotherapy alone or combined with immunotherapy. * Osteosarcoma: Patients must have received frontline therapy and at least one prior line of relapse systemic anticancer therapy for relapsed or refractory disease. Patients with an isolated relapse manifestation (lung metastasis or local relapse) must have unresectable disease. * Ewing sarcoma: Patients must have received frontline therapy and at least one prior line of relapse chemotherapy according to standard regimens. Patients with an isolated lung relapse must have received pulmonary irradiation during frontline or relapse therapy. * All participants must additionally meet the following criteria: * GD2 expression on tumor cells in an archival biopsy assessed by the central reference laboratory. GD2-positive tumor is defined as GD2 at least 50% of tumor cells expressing GD2 at an intensity of 2+ or higher, using an immunofluorescence assay for specific detection of GD2 expression in formalin-fixed, paraffin-embedded or frozen tumor tissue with semiquantitative evaluation. * Evaluable disease based on Response Evaluation Criteria in Solid Tumors for all disease entities or, in cases of diffuse bone/bone marrow metastases, by whole-body nuclear medicine imaging (e.g. metaiodobenzylguanidine (MIBG)) scan for neuroblastoma or positron emission tomography (PET) based imaging. * Age ≥1 year and ≤25 years. * Absolute cluster of differentiation 3 (CD3)-positive T-cell count ≥200/µL. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 for participants \>16 years of age or Lansky performance score ≥60 for participants ≤16 years of age at screening. * No childbearing potential, or negative pregnancy test at screening and before chemotherapy in participants with childbearing potential. * Signed and dated informed consent/assent by participants and/or their caregivers before any trial-specific procedure. Exclusion Criteria: * Active solid central nervous system (CNS) metastases or metabolically active metastatic disease in the skull with direct contact to the dura. * Current autoimmune disease or history of autoimmune disease with potential CNS involvement. * Active clinically significant CNS dysfunction, including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, or paralysis. * History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for ≥3 years. * Pre-existing severe lung disease, oxygen requirement of \>28% inspired oxygen (O2) supplementation, or active pulmonary infiltrates on X-ray. * Cardiac function: Pediatric patients (˂18 yrs): fractional shortening \