Participants with relapsed or refractory hematologic malignancies will receive ENTO twice daily of every 28-day cycle until participants meet treatment discontinuation criteria or do not experience clinical benefit.

Lead-in (Cycle 0): Participants with previously untreated AML will receive ENTO twice daily for 14 days.

Induction (Up to 2 cycles): ENTO in combination with daunorubicin and cytarabine for up to two 28-day cycles.

Post-remission chemotherapy (at least 2 cycles, up to 4 cycles): Some participants (who have achieved complete remission [CR] or morphologic complete remission with incomplete blood count recovery [CRi] and do not require or cannot proceed to allogeneic stem cell transplantation [SCT] and participants who are awaiting a donor or transitioning to allogeneic SCT per investigator discretion) will have the option to receive post-remission chemotherapy with ENTO twice daily in combination with high-dose cytarabine (Hi-DAC) for up to four 28-day cycles.

400 mg (2 × 200 mg tablets) orally twice daily

Occurrence of any of the following toxicities, attributable to ENTO, during Cycle 1 was considered DLT:

• Grade 4 non-hematologic toxicity except alopecia, nausea, and vomiting controllable with anti-emetic therapy, line associated venous thrombosis, infection-related toxicities such as fever/sepsis, and fatigue.
• In participants without bone marrow evidence of hematologic malignancy, hematologic toxicity defined as failure to recover absolute neutrophil count (ANC > 500/μL) or platelet count (>25000/μL) within 28 days
• Grade 4, clinically significant, electrolyte abnormalities that were not correctable within 24 hours
• Liver function test abnormalities that did not resolve to Grade 2 within 10 days
• Infection that resulted from unexpectedly complicated prolonged myelosuppression
• Toxicities that required temporary interruption of treatment and did not resolve to Grade 2 within 10 days or ENTO was suspended or dose reduced for a period of more than 10 days.

Plasma concentration of drug (ENTO) over different time points is reported.

Participants received ENTO 400 mg (2 × 200 mg tablets) orally twice daily in a fasted state on Days 1 through 28 of every 28-day cycle, and continued on study treatment as long as the participant experienced benefit and did not meet the criteria for study treatment discontinuation.

Occurrence of any of the following toxicities, attributable to ENTO, during Cycle 1 was considered DLT:

• Grade 4 non-hematologic toxicity except alopecia, nausea, and vomiting controllable with anti-emetic therapy, line associated venous thrombosis, infection-related toxicities such as fever/sepsis, and fatigue.
• In participants without bone marrow evidence of hematologic malignancy, hematologic toxicity defined as failure to recover absolute neutrophil count (ANC > 500/μL) or platelet count (>25000/μL) within 28 days
• Grade 4, clinically significant, electrolyte abnormalities that were not correctable within 24 hours
• Liver function test abnormalities that did not resolve to Grade 2 within 10 days
• Infection that resulted from unexpectedly complicated prolonged myelosuppression
• Toxicities that required temporary interruption of treatment and did not resolve to Grade 2 within 10 days or ENTO was suspended or dose reduced for a period of more than 10 days.

The DLT Analysis Set included all participants in the Full Analysis Set (all participants who received at least 1 dose of study drug [ENTO]) who received at least 21 days of ENTO or experienced a DLT during DLT assessment window.

Participants received ENTO 400 mg (2 × 200 mg tablets) orally twice daily in a fasted state on Days 1 through 28 of every 28-day cycle, and continued on study treatment as long as the participant experienced benefit and did not meet the criteria for study treatment discontinuation.