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