Inclusion Criteria:
- Tumor characteristics of participants in Phase 1
1. Histologically and/or cytologically confirmed diagnosis of advanced or metastatic solid tumor and/or non-Hodgkin lymphoma excluding primary central nervous system malignancy for which no standard effective treatment exists or where that treatment was declined. Participants with non-Hodgkin lymphoma should have failed ≥ 2 prior lines of systemic therapy prior enrollment.
2. Tumor p53 wild-type.
- Tumor characteristics of participants in Phase 2a
1. Cohort A: Tumor p53 wild-type with histologically confirmed diagnosis of advanced or metastatic DD LPS (and MDM2 amplification); OR Cohort B: Tumor p53 wild-type in other solid tumor.
2. Measurable disease by RECIST 1.1.
- 18 years old or older.
- Resolution of clinically relevant toxicity-related to prior anticancer therapies prior to receipt of study treatment to Grade 1 or less.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participants of childbearing/reproductive potential must agree to use adequate birth control measures during the course of the trial and for at least 3 months after discontinuing study treatment.
Exclusion Criteria:
- Anticipated need for major surgery and/or localized palliative radiation within the next 6 weeks
- Active, untreated central nervous system metastases. Participants with brain metastases identified at Screening may be rescreened after the lesion(s) have been appropriately treated; participants with treated brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study enrollment, and off corticosteroids for at least 2 weeks before start of study treatment, and treated lesions should demonstrate no new growth on the re-screening scan.
- Known HIV infection or active hepatitis B or C infection.
- Thrombotic event requiring active and ongoing anticoagulation within the last 6 months prior to study treatment.
- Myocardial infarction within the last 6 months prior to study treatment.
- Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, congestive heart failure New York Heart Association (NYHA) Class III or IV related to primary cardiac disease, uncontrolled ischemic or severe vascular heart disease.
- A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
- Known bleeding disorder (e.g., hemophilia, von Willebrand disease).
- Conditions that may predispose to major bleeding (e.g., active GI ulcers, upper or lower GI bleedings in the last 6 months, significant hemoptysis in the last 6 months, tumor invasion of major vessels, etc.). Conditions that have been treated may be allowed if resolution of the risk is documented.
- Use or indication for full dose anticoagulation or anti-platelet therapy including low dose aspirin.
- Women who are pregnant or lactating.