WALTHAM, Massachusetts, USA, June 2, 202
Stelexis BioSciences has announced encouraging Phase 1 clinical trial results for eganelisib, its investigational oral PI3K-gamma inhibitor, in patients with relapsed/refractory acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). Presented during an oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, the study demonstrated that eganelisib induced complete remissions, hematologic improvements, and meaningful survival benefits in a heavily pretreated patient population with historically poor outcomes. The findings highlight the potential of targeting PI3K-gamma, a newly identified biological vulnerability in myeloid malignancies, while also establishing a biomarker-driven approach that may help identify patients most likely to benefit from treatment. With limited therapeutic options available for patients who relapse after standard therapies, the data position eganelisib as a promising candidate in an area of significant unmet medical need.
Biomarker-Driven Responses Demonstrate Clinical Potential
The Phase 1 study enrolled 21 patients with relapsed or refractory AML or higher-risk MDS, many of whom carried adverse prognostic features including TP53 mutations, abnormal cytogenetics, prior venetoclax exposure, and multiple previous treatment failures. Researchers observed a 50% modified objective response rate among patients with high PI3K-gamma expression, compared with no responses in patients with low expression levels. Responses included complete remissions as well as molecular and major cytogenetic remissions, suggesting substantial anti-leukemic activity.
Importantly, investigators identified PI3K-gamma expression as a predictive biomarker, allowing clinicians to potentially select patients most likely to respond to therapy. This precision medicine approach could represent a significant advancement for myeloid malignancies, where treatment decisions have traditionally relied primarily on disease classification and risk scoring systems rather than actionable biological targets.
Eganelisib Improves Survival and Promotes Myeloid Differentiation
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One of the most compelling findings from the study was the improvement in overall survival among patients with elevated PI3K-gamma expression. Median overall survival reached 27 weeks in PI3K-gamma-high patients, compared with only 9.9 weeks among low expressors, representing a substantial clinical benefit in a population known for poor outcomes. Investigators also observed rapid improvements in neutrophil counts among responding patients, including normalization of neutrophil levels in several individuals who entered the study with severe or life-threatening neutropenia.
These findings support the proposed mechanism of action, in which eganelisib promotes myeloid differentiation, helping malignant cells mature into functional blood cells rather than remaining trapped in an immature leukemic state. Researchers noted that external validation from The Cancer Genome Atlas (TCGA) database confirmed that high PI3K-gamma expression is typically associated with worse survival under conventional treatment, further strengthening the significance of the observed clinical benefit.
Favorable Safety Profile Supports Future Development
In addition to demonstrating efficacy, eganelisib showed a favorable safety and tolerability profile throughout the study. No dose-limiting toxicities were reported at either evaluated dose level, and investigators observed no intrinsic hematologic toxicity, an important consideration for patients already experiencing severe bone marrow dysfunction. Most adverse events were related to underlying disease rather than treatment, while treatment-related events were generally low grade and manageable. Notably, no patients discontinued therapy due to eganelisib-related adverse events, and no treatment-related serious adverse events were reported.
Based on the positive results, Stelexis plans to advance the program into a randomized expansion study evaluating eganelisib in combination with hypomethylating agents in treatment-naïve patients with PI3K-gamma-high higher-risk MDS and CMML-2. The company believes PI3K-gamma may represent a transformative therapeutic target in myeloid malignancies, similar to the role HER2 plays in breast cancer. If future studies confirm these findings, eganelisib could emerge as a first-in-class targeted therapy capable of changing the treatment landscape for patients with AML and MDS who currently face limited options and poor long-term survival prospects.
Source: Stelexis BioSciences press release
