Eganelisib as Monotherapy and in Combination With Cytarabine in Relapsed/Refractory AML/HR-MDS and in Combination With Azacitidine in Previously Untreated HR-MDS

Prior treatment

• Autologous or allogeneic stem cell transplant within 6 months prior to Cycle 1 Day 1.
• Receiving immunosuppressants (eg, cyclosporin) or systemic steroids (except for steroid use as cortisol replacement therapy in documented adrenal insufficiency).
• Active fungal disease or uncontrolled infection of any kind; patients receiving antibiotic, antifungal or antiviral treatment must be afebrile and hemodynamically stable for \>72 hours prior to treatment
• Presence of a clinically significant non-hematologic toxicity of prior therapy that has not resolved to Grade ≤1 or Baseline, whichever is worst, as determined by NCI CTCAE v 5.0, except alopecia or skin pigmentation. Fatigue and neuropathy must have resolved to Grade ≤2.

Lab values

• WBC count \>25 × 10\^9/L measured within 7 days prior to the first dose of eganelisib (hydroxyurea is permitted to decrease the WBC count).

• Part 1: Pathological diagnosis of either: AML according to World Health Organization (WHO) 2022 revised criteria per the local pathology report and with ≥10% bone marrow blasts (acute promyelocytic leukemia is excluded but secondary AML and treatment-related AML can be included); Higher-risk (IPSS-R Intermediate, High or Very High Risk at time of study entry) myelodysplastic syndromes (HR-MDS) according to WHO 2022 revised criteria per the local pathology report and with ≥10% bone marrow blasts.
• Part 2: Pathological diagnosis of previously untreated HR-MDS according to WHO 2022 revised criteria, with bone marrow blasts ≥5% and \<20%; Moderate or higher PI3K-Gamma in bone marrow blasts, as determined by an IHC assay; Deemed by the Investigator to require frontline therapy with azacitidine.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Adequate hepatic and renal function measured within 7 days prior to the first dose of eganelisib.