Domatinostat With Sirolimus for Relapsed, Refractory Sarcoma and Osteosarcoma

Inclusion Criteria: * Age ≥12 and ≤40 years. * Histologically confirmed relapsed or refractory sarcoma (Phase 1) or osteosarcoma (Phase 2). * At least one prior standard systemic therapy regimen. * Not candidates for available therapies known to provide survival benefit. * Karnofsky/Lansky performance score ≥60. * Life expectancy ≥16 weeks. * Adequate organ function: ANC ≥1,000/mcL, Platelets ≥100,000/uL, Hemoglobin ≥8 g/dL, Adequate hepatic and renal function. * Ability to swallow tablets. * Negative pregnancy test for females of childbearing potential. * Agreement to use effective contraception. * Ability to provide informed consent/assent. Exclusion Criteria: * Receiving another investigational agent. * Receiving concurrent anticancer therapy. * Known hypersensitivity to domatinostat or sirolimus. * Bone marrow-only disease. * CNS metastatic disease. * Major surgery within 2 weeks prior to treatment. * Active malignancy within the previous 3 years (with protocol-specified exceptions). * History of solid organ transplantation. * Significant recent cardiac disease. * Concurrent prohibited CYP3A4/P-gp interacting medications. * Uncontrolled infection or other serious uncontrolled illness. * Pregnancy or breastfeeding. * HIV infection on antiretroviral therapy. * Weight \<40 kg. * Inability to comply with study requirements.