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

Stelexis BioSciences

Status and phase: Enrolling; Phase 1

Conditions: MDS; AML, Adult

Treatments: Drug: Eganelisib in combination with azacitidine; Drug: Eganelisib; Drug: Azacitadine (AZA); Drug: Eganelisib in combination with cytarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT06533761

STLX-EGA-001

Details and patient eligibility

About

This is a Phase 1b open-label, multicenter, dose-escalation and randomized combination cohort 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) and in combination with azacitidine in PI3K-Gamma-Positive patients with previously untreated HR-MDS.

The study consists of 2 parts:

• Part 1: Dose Escalation (DE) in both monotherapy and in combination with cytarabine.
• Part 2: Randomized Combination Cohort: eganelisib + azacitidine and azacitidine alone

Enrollment: 105 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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105 participants in 4 patient groups

Eganelisib

Experimental group

Treatment:

Drug: Eganelisib

Eganelisib in combination with cytarabine

Experimental group

Treatment:

Drug: Eganelisib in combination with cytarabine

Eganelisib in combination with azacitidine

Experimental group

Treatment:

Drug: Eganelisib in combination with azacitidine

Azacitidine

Active Comparator group

Treatment:

Drug: Azacitadine (AZA)