Clinical Summary:

• Design/Population: This phase 1 study evaluated single-agent eganelisib, a selective PI3Kγ inhibitor, in heavily pretreated patients with relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndromes, most of whom had adverse-risk disease and prior venetoclax exposure.
• Key Outcomes: Eganelisib demonstrated target inhibition and preliminary antileukemic activity, including a complete response and evidence of clinical benefit in heavily pretreated patients.
• Clinical Relevance: These findings support PI3Kγ as a potential therapeutic target and provide rationale for future combination studies with venetoclax and nucleoside analogues.

According to results from a phase 1 study, eganelisib, a selective PI3Kγ inhibitor, showed preliminary single-agent activity with manageable safety among heavily pretreated patients with relapsed or refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). 

These results were presented by Mendel Goldfinger, MD, Montefiore Medical Center, Bronx, New York, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

In this multicenter study, researchers enrolled 15 patients with either relapsed or refractory AML (n = 14) or intermediate- to very high-risk MDS (n = 1) with at least 10% bone marrow blasts who received a median of 2 prior lines of therapy. Patients received either 45 mg (n = 7) or 60 mg (n = 8) of once daily eganelisib in 28-day cycles. The primary end points were safety and efficacy. Key secondary end points included pharmacokinetics and pharmacodynamics. 

At analysis, no dose-limiting toxicities were observed at either dose level. Pharmacodynamic analyses demonstrated dose-dependent target engagement of AKT phosphorylation, with approximately 90% suppression observed at the 60 mg dose.

Among 10 patients who completed at least one 28-day cycle, evidence of anti-leukemic activity was observed in 4 patients. One patient treated at 45 mg achieved a complete response. At the 60 mg dose, 1 patient achieved <5% bone marrow blasts by flow cytometry, a major cytogenetic response, rapid subclonal clearance, and full trilineage count recovery despite low levels of persistent circulating blasts. Two additional patients with TP53-mutated disease experienced stable or decreasing marrow blast counts accompanied by rising neutrophil counts during treatment. The longest treatment duration reported exceeded 5 cycles.

The safety profile was consistent with prior experience with eganelisib. Drug exposure was variable across dose levels, although both doses produced overlapping plasma concentrations. Investigators reported no intrinsic hematologic toxicity.

“Given the capacity to potentiate activity of nucleoside analogues and venetoclax, combined therapy in previously untreated [high-risk MDS and AML] patients at the [recommended expansion dose] of 60 mg QD is planned,” concluded Dr Goldfinger. 

Source:

Goldfinger M, Advani AS, Vicente IN, et al. Safety and efficacy of eganelisib in adults with higher-risk myelodysplastic syndrome (HR-MDS) or relapsed/refractory (R/R) acute myeloid leukemia (AML). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 6507.