Inclusion Criteria:  Phase 1b and Phase 2 Arms A and B: Documented TP53wt, Ph+, BCR-ABL+ CML-CP Phase 2 Arm C ONLY: Documented TP53wt, Ph+, BCR-ABL+ CML-AP Subject is resistant (relapsed or refractory) and/or intolerant to at least 2 prior TKIs. Adults ≥ 18 years of age. ECOG performance status of 0 to 2 Adequate hematologic, hepatic, and renal functions  Exclusion Criteria:  Phase 1b and Phase 2 Arms A and B: Documented Ph+, BCR-ABL+ CML-AP Documented Ph+, BCR-ABL+ CML-BC Known history of T315I mutation. Prior treatment with MDM2 antagonist therapies. Intolerance to current TKI therapy.