Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma

Inclusion Criteria: * Histologically confirmed DD liposarcoma, with or without a WD component (WD/DD liposarcoma). Note: Patient must be willing to provide an archival tumor tissue sample that is ≤ 3 years old and of adequate quality or willing to provide a fresh pretreatment biopsy sample * Advanced unresectable (i.e., where resection is deemed to cause unacceptable morbidity or mortality) and/or metastatic WD/DD liposarcoma * Measurable tumor lesion(s) in accordance with RECIST version 1.1 * Received 1 or more systemic cancer therapy regimens, including at least 1 anthracycline-based regimen, and had radiographic progressive disease (per RECIST version 1.1) within 6 months before the Screening Visit * Resolution of any clinically relevant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy * ECOG performance status of 0 or 1 * Adequate bone marrow function: * Platelet count ≥ 100 × 10\^9/L * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count ≥ 1.5 × 10\^9/L * Adequate hepatic function: * Alanine aminotransferase and aspartate aminotransferase ≤ 3 × upper limit of normal (ULN) if no liver metastases are present; ≤ 5 × ULN if liver metastases are present * Total bilirubin ≤ 1.5 × ULN, or ≤ 3 x ULN in the setting of Gilbert's disease Exclusion Criteria: * Prior treatment with any mouse double minute 2 (MDM2) inhibitor or trabectedin * Other primary malignancies that have required systemic antineoplastic treatment within the previous 2 years, except for localized cancers that have apparently been cured * Gastrointestinal conditions that could affect the absorption of milademetan, in the opinion of the Investigator * Uncontrolled infection within the last 7 days requiring IV antibiotics, antivirals, or antifungals * Known HIV infection or active Hepatitis B or C * Untreated brain metastases. Note: Patients who require steroids for brain metastases must be on a stable or tapering dose of corticosteroids for at least 2 weeks before randomization. If applicable, patients must complete stereotactic radiosurgery 7 days before and whole brain radiotherapy 21 days before their first dose of study drug. * Investigational therapy administered within the 28 days or 5 half lives: 1. Cytochrome P450 3A4 isozyme strong inhibitor: 5 elimination half-lives 2. CYP3A strong or moderate inducers: 4 weeks 3. Systemic anticancer therapy or investigational therapy 3 weeks or 5 half-lives, 4. Immunotherapy with checkpoint inhibitor: 4 weeks * Curative-intent radiation therapy ≤ 4 weeks or palliative radiation therapy, * Uncontrolled or significant cardiovascular disease: 1. QTcF at rest, where the mean QTcF interval is \> 480 milliseconds 2. Myocardial infarction within 6 months 3. Uncontrolled angina pectoris within 6 months 4. New York Heart Association Class 3 or 4 congestive heart failure 5. Uncontrolled hypertension