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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stelexis Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

16 May 2025 → ongoing

Decision date (initial)

2025-04-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Stelexis BioSciences Inc.

External identifiers

EU CT number

2024-518071-58-00

ClinicalTrials.gov

NCT06533761

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Dose response, Pharmacokinetic, Efficacy

Part 1 – Monotherapy and Combination Dose Escalation (DE):
• Assess the safety and tolerability of eganelisib administered as monotherapy and in combination with cytarabine
• Determine the recommended dose for expansion (RDE) of eganelisib as monotherapy and in combination with cytarabine
Part 2 – Dose Optimization (OPT):
• Evaluate preliminary clinical activity of eganelisib administered as monotherapy and in combination with cytarabine

Secondary objectives 7

1. Part 1 – Monotherapy and Combination Dose Escalation (DE): Evaluate the preliminary clinical activity of eganelisib administered as monotherapy and in combination with cytarabine
2. Part 1 – Monotherapy and Combination Dose Escalation (DE): Characterize the plasma pharmacokinetics (PK) of eganelisib administered as monotherapy and in combination with cytarabine
3. Part 1 - Combination DE ONLY: Characterize the plasma PK of cytarabine in combination with eganelisib
4. Part 2 – Dose Optimization (OPT): Assess the safety and tolerability of eganelisib administered as monotherapy and in combination with cytarabine
5. Part 2 – Dose Optimization (OPT): Determine the recommended Phase 2 dose (RP2D) of eganelisib administered as monotherapy and in combination with cytarabine
6. Part 2-Dose Optimization (OPT): Evaluate further the preliminary clinical activity of eganelisib administered as monotherapy and in combination with cytarabine
7. Part 2 Dose Optimization (OPT): Measure plasma concentrations of eganelisib and determine model-based PK parameters

Conditions and MedDRA coding

Relapsed/refractory (r/r) acute myeloid leukemia (AML) or r/r higher-risk myelodysplastic syndromes (HR-MDS)

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Provision of written informed consent.
2. Pathological diagnosis of either - AML according to WHO 2022 revised criteria (Khoury et al., 2022) per the local pathology report and with ≥10% bone marrow blasts. Acute promyelocytic leukemia is excluded but secondary AML (including “treated secondary AML”, i.e., treatment included a hypomethylating agent [HMA] based therapy for MDS but transformed into 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.
3. Relapsed/refractory disease. Patients must not be eligible for, or must have exhausted, other therapies known to be effective for treatment of their disease. - Hydroxyurea administered for white blood cell (WBC)/blast control will not be considered a prior line of therapy. - Treatments with erythroid-stimulating agents (eg, EPO, luspatercept, lenalidomide) will not be considered a prior line of therapy.
4. Male or female patients age ≥18 years.
5. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2.
6. Adequate hepatic function measured within 7 days prior to the first dose of eganelisib: - Total serum bilirubin ≤1.5 × institutional upper limit of normal (ULN) or ≤3 × ULN in case of Gilbert’s disease. -AST and ALT ≤2.5 × ULN.
7. Adequate renal function measured within 7 days prior to the first dose of eganelisib: Measured or calculated creatinine clearance (CrCl) ≥30 mL/min (calculation by Cockcroft-Gault formula).
8. Acceptable coagulation profile, measured within 7 days prior to the first dose of eganelisib: - Prothrombin time (PT) or International Normalized Ratio (INR) ≤1.5 × ULN. - Activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
9. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures, including to undergo a pre-treatment and subsequent on treatment bone marrow examinations.
10. Male patients and female patients/women of childbearing potential (WCBP) must agree to use an effective method of contraception per institutional standard for the study duration and for 30 days after the last dose of eganelisib and 6 months after the last dose of cytarabine.
11. WCBP must have a negative serum beta human chorionic gonadotropin (β HCG) test measured within 7 days prior to the first dose of eganelisib and consent to ongoing pregnancy testing during the study.
12. Willingness to practice adequate sun protection (use of sunscreen or sun-protective clothing, limitation of sun and artificial ultraviolet [UV] exposure) for the study duration and for 30 days after the last dose of eganelisib.

Exclusion criteria 13

1. Any of the following within the specified time frame: -Prior systemic cancer therapy is allowed regardless of the stop date, but the patient must have recovered to eligibility levels from prior toxicity. --> Hydroxyurea is allowed for patients with rapidly proliferative disease for peripheral blast control, up to Cycle 1 Day 7. - Major surgery within 28 days prior to Cycle 1 Day 1. - Autologous or allogeneic stem cell transplant within 6 months prior to Cycle 1 Day 1. - Receiving immunosuppressants (eg, cyclosporin or calcineurin inhibitors) or systemic steroids (except for steroid use as cortisol replacement therapy in documented adrenal insufficiency or low-dose steroids with a maximum of an equivalent of 10 mg prednisone/day) within 28 days prior to Cycle 1 Day 1. - 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. - Active graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, or chronic GVHD requiring systemic steroid administration. - Current use (including within 5 half-lives) of an investigational agent.
2. 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).
3. 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, except alopecia or skin pigmentation. Fatigue and neuropathy must have resolved to Grade ≤2.
4. History of another primary malignancy that is currently clinically significant or currently requires active intervention.
5. Known hypersensitivity to any excipient in the study drugs.
6. Pregnant or lactating female.
7. Known central nervous system (CNS) leukemia.
8. Known isolated extramedullary disease.
9. Significant gastrointestinal abnormalities, including requirement for IV alimentation, active peptic ulcer, chronic diarrhea or vomiting considered to be clinically significant in the judgment of the Investigator, or malabsorption syndrome or prior surgical procedures affecting drug absorption (eg, gastric bypass surgery, gastrectomy).
10. History or current evidence of any acute or chronic condition, therapy, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or might confound the results of the trial, interfere with participation for the full duration of the trial, or render trial participation not compatible with the patient’s best interest, in the opinion of the Investigator.
11. Administration of any of the following within 14 days prior to the first dose of eganelisib and for the study duration: - Moderate or strong inhibitors or inducers of CYP2C8 and CYP3A4, including grapefruit, grapefruit juice, Seville oranges, St. John’s wort and herbal supplements, except for antibiotics, antifungals, or antivirals that are moderate or strong inhibitors of CYP3A if they cannot be avoided. - P-glycoprotein (P-gp) inhibitors, except for antibiotics, antifungals, or antivirals if they cannot be avoided. - Breast cancer resistance protein (BCRP) inhibitors.
12. Administration of any of the following as of Cycle 1 Day 1 and for the study duration: - P-gp substrates with a narrow therapeutic index. - Warfarin, phenytoin, or other CYP2C8 or CYP2C9 substrates with a narrow therapeutic index.
13. Corrected QT with Fridericia’s method (QTcF) interval on screening electrocardiogram (ECG) ≥450 msec for males and ≥470 msec for females, except for patients with atrioventricular pacemakers or other conditions (eg, right bundle branch block) that render the QT measurement invalid.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1 – Monotherapy and Combination Dose Escalation (DE): Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0
2. Part 1 – Monotherapy and Combination Dose Escalation (DE): Incidence and severity of dose-limiting toxicities (DLTs) in DLT-evaluable patients during Cycle 1
3. Part 2 – Dose Optimization (OPT): AML: per ELN 2022 criteria CR rate
4. Part 2 – Dose Optimization (OPT): HR-MDS: per IWG 2023 criteria CR rate, defined as CR + CR equivalent

Secondary endpoints 10

1. Part 1 – Monotherapy and Combination Dose Escalation (DE): AML: per European LeukemiaNet (ELN) 2022 criteria (Dohner et al., 2022); Complete response [CR] rate; Composite CR (CR + CRh); Composite CRMRD- (CRMRD- + CRhMRD-); ORR (CR + CRi + CRh + partial response [PR] + morphologic leukemia-free status [MLFS]); Duration of response; Time to CR, time to composite CRs; Transfusion-independence (TI); Duration of TI
2. Part 1 – Monotherapy and Combination Dose Escalation (DE): HR-MDS: per International Working Group (IWG) 2023 criteria (Zeidan et al., 2023); CR rate, defined as CR + CR equivalent; ORR (CR + CR equivalent + CRh + CRL + PR + hematologic improvement [HI]); Duration of response; Time to CR; TI; Duration of TI
3. Part 1 – Monotherapy and Combination Dose Escalation (DE): Both AML and HR-MDS: Frequency of transition to allogeneic hematopoietic stem cell transplant (HSCT); Early death rate; Event-free survival (EFS); Overall survival (OS)
4. Part 1 – Monotherapy and Combination Dose Escalation (DE): Noncompartmental PK parameters of eganelisib (eg, area-under-the-curve [AUC0-24h, AUC0-͚∞], maximum concentration [Cmax], time of Cmax [Tmax], half-life [t1/2])
5. Part 1 – Combination Dose Escalation (DE): Noncompartmental PK parameters of cytarabine (eg, Cmax, Tmax, AUC, possibly t1/2, volume of distribution [Vd], and clearance [CL])
6. Part 2 – Dose Optimization (OPT): Incidence and severity of AEs, graded according to the NCI CTCAE, Version 5.0
7. Part 2 – Dose Optimization (OPT): AML: per ELN 2022 criteria: Composite CR (CR + CRh); Composite CRMRD- (CRMRD- + CRhMRD-); ORR (CR + CRi + CRh + PR + MLFS); Duration of response; Time to CR: time to composite CRs; TI; Duration of TI
8. Part 2 – Dose Optimization (OPT): HR-MDS: per IWG 2023 criteria: ORR (CR + CR equivalent + CRh + CRL + PR + HI); Duration of response; Time to CR; TI; Duration of TI
9. Part 2 Dose Optimization (OPT): Both AML and HR-MDS; Frequency of transition to allogeneic HSCT; Early death rate; EFS; OS
10. Part 2 Dose Optimization (OPT): Plasma concentrations and population pharmacokinetic (PopPK) assessment of possible covariates of exposure, safety, and efficacy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stelexis Biosciences Inc.

Sponsor organisation

Stelexis Biosciences Inc.

Address

345 Park Avenue South Floor 12th

City

New York

Postcode

10010-1707

Country

United States

Scientific contact point

Organisation

Stelexis Biosciences Inc.

Contact name

Deepa Deshpande

Public contact point

Organisation

Stelexis Biosciences Inc.

Contact name

Eric Feldman

Third parties 17

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications