Eganelisib as Monotherapy and in Combination With Cytarabine in Relapsed/Refractory AML

A Phase 1b Open-Label Study to Evaluate the Safety and Tolerability of Eganelisib as Monotherapy and in Combination With Cytarabine in Patients With Relapsed/Refractory Acute Myeloid Leukemia

This is a Phase 1b open-label, multicenter, dose-escalation and dose-optimization study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor efficacy of eganelisib as monotherapy and in combination with cytarabine in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML) or r/r higher-risk myelodysplastic syndromes (HR-MDS).

The study consists of 2 parts:

• Part 1: Dose Escalation (DE) in both monotherapy and in combination.
• Part 2: Dose Optimization

Inclusion Criteria:

• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Adequate hepatic and renal function measured within 7 days prior to the first dose of eganelisib.

Exclusion Criteria:

• 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
• 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).
• 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.