2.5 Safety and Efficacy Assessments
Routine clinical and laboratory assessments, physical examinations,
EKGs, echocardiograms, and tibial growth plate x-rays were conducted at
baseline and prespecified intervals. Adverse events were graded using
National Cancer Institute Common Terminology Criteria for Adverse Events
(CTCAE), version 5. Imaging studies and tumor assessments were obtained
at baseline, after cycle 2, after cycle 4, and then every 4 cycles until
documented progression for patients with complete response (CR), partial
response (PR), or stable disease (SD). Response was assessed using
Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version
1.1). Patients with an overall best objective response of CR or PR prior
to any local measures were categorized as responders, and all other
patients as non-responders.
2.6 Correlative Biology Evaluations
Serial plasma samples were obtained to quantify and characterize ctDNA
over time in response to protocol therapy. Peripheral blood samples were
collected in cell-stabilizing tubes at baseline, Cycle 1 Day 3, Cycle 1
Day 5, Cycle 2 Day 1, and then at times of subsequent of disease
evaluation. Plasma was isolated and processed to collect cell free DNA
as previously described [18]. TranSS-Seq to detect EWSR1 andFUS fusions was used to quantify ctDNA for patients with Ewing
sarcoma and ultra-low passage whole genome sequencing (ULP-WGS) to
detect aneuploidy was used for patients with osteosarcoma. Detailed
methods are as previously reported [18].