Trastuzumab Deruxtecan for the Treatment of HER2+ Newly Diagnosed or Recurrent Osteosarcoma

Inclusion Criteria: * Patients must be \> 12 years and =\< 39 years of age at the time of study enrollment * Patients must have had histologic verification of osteosarcoma at original diagnosis or relapse * Patients with diagnoses of osteosarcoma and confirmed HER2 expression of \> 10% of osteosarcoma cells are eligible for the intervention * Note: There is a mandatory tissue submission for HER2 staining during the Step 0 Eligibility Screening process. Metastatic tissue, when possible from the most recent relapse, is strongly preferred for HER2 staining over archival tissue from primary resection or diagnostic biopsy. The evaluation period for HER2 staining to determine eligibility for therapy will be less than 4 weeks from screening enrollment * Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients with clinically inactive brain metastases may be included in the study. Patients with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Lastly, patient must have unresectable lesions or lesions with no intention to surgically remove in the 6 months following enrollment * Patient's current disease state must be one for which they have received at least standard initial therapy, defined as systemic therapy combined with either radiation or s…