Correlative Studies for Protocol #14-C-0059: T Cells Expressing an Anti-GD2 Chimeric Antigen Receptor in Patients with GD2+ Solid Tumors, a Collaboration with CIMAC-CIDC

This study is a retrospective correlative analysis of immune cell phenotypes in samples from a Phase I clinical trial (NCT02107963) of GD2 CAR-T cells (GD2-CAR.OX40.28.z.iC9) in children and young adults with osteosarcoma and neuroblastoma. The study was a 3+3 dose-escalation study with four dose levels (1 x 10(5) transduced T cells/kg; 1 x 106 transduced T cells/kg; 3 x 106 transduced T cells/kg; and 1 x 107 transduced T cells/kg). Apheresis and final manufactured GD2 CAR-T product samples were analyzed by bulk RNA sequencing and ATAC sequencing. The patients were stratified into good CAR-T expanders (peak CAR-T expansion >1000 GD2 CAR copies/100ng DNA) and poor CAR-T expansion (peak CAR-T expansion <1000 GD2 CAR copies/100ng DNA). The principal findings of the study are: Increased naïve T cell subsets in baseline apheresis are associated with patients who experienced good CAR T cell expansion A T cell exhaustion signature was observed in the manufactured GD2 CAR-T product and may have contributed to lack of efficacy observed in this trial Increased myeloid-derived suppressor cell (MDSC) signatures were observed in patients with poor CAR-T expansion CAR-T product in good expanders displayed increased AP-1 factor transcription factor motifs, such as BATF, JUN, and FOS Data provided in dbGaP for this study include: Bulk RNA-Seq data for 11 pre-treatment peripheral blood and 11 GD2 CAR-T product from 14 patients. ATAC sequencing of 22 peripheral blood samples and 5 GD2 CAR-T products from 14 patients. ]]>
All patients enrolled in the original protocol that had collected samples available were included in these correlative studies. Full inclusion/exclusion criteria can be found on clinicaltrials.gov. A brief listing of important criteria is as follows: INCLUSION CRITERIA: Diagnosis Osteosarcoma, neuroblastoma and melanoma that have been treated with standard frontline therapy and are judged to be incurable with standard therapy, based upon the fact that they are unresectable, metastatic, progressive/persistent or recurrent Evaluable disease must be present. Weight greater than or equal to 15 kg Age less than or equal to 35 years old at the time of enrollment Prior Therapy: The patient's malignancy must have relapsed after, or failed to respond to, frontline curative therapy and/or there must not be any curative treatment options available at the time of study entry There is no limit to the number of prior treatment regimens ECOG 0, 1 or 2, or for children less than or equal to 10 years of age, Lansky greater than or equal to 60 EXCLUSION CRITERIA: Concurrent Illnesses Untreated CNS metastasis Prior Therapy Previous treatment with genetically engineered GD2-CAR T cells. Previous vaccine therapy, anti-GD2 mAb therapy or therapy with other genetically engineered T cells is not an exclusion criteria. Lactating or pregnant females (due to risk to fetus or newborn) Active HIV, HBV or HCV infection Immune Therapies INCLUSION OF WOMEN AND MINORITIES: Both men and women of all races and ethnic groups are eligible for this trial. ]]>
Patient enrollment began in February, 2014 and was completed in May, 2016. ]]>