EGANELISIB for Acute myeloid leukemia (relapsed/refractory) | High-risk myelodysplastic syndromes (relapsed/refractory)

Inclusion criteria

• {"criterion_text":"- Provision of written informed consent.\n- 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.\n- 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.\n- 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.\n- 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.\n- Relapsed/refractory disease. Patients must not be eligible for, or must have exhausted, other therapies known to be effective for treatment of their disease. \t- Hydroxyurea administered for white blood cell (WBC)/blast control will not be considered a prior line of therapy. \t- Treatments with erythroid-stimulating agents (eg, EPO, luspatercept, lenalidomide) will not be considered a prior line of therapy.\n- Male or female patients age ≥18 years.\n- Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2.\n- 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.\n- 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).\n- 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.\n- 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."}

Exclusion criteria

• {"criterion_text":"- 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. \t- 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.\n- 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.\n- 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.\t- Breast cancer resistance protein (BCRP) inhibitors.\n- Administration of any of the following as of Cycle 1 Day 1 and for the study duration: \t- P-gp substrates with a narrow therapeutic index. \t- Warfarin, phenytoin, or other CYP2C8 or CYP2C9 substrates with a narrow therapeutic index.\n- 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.\n- 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).\n- 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.\n- History of another primary malignancy that is currently clinically significant or currently requires active intervention.\n- Known hypersensitivity to any excipient in the study drugs.\n- Pregnant or lactating female.\n- Known central nervous system (CNS) leukemia.\n- Known isolated extramedullary disease.\n- 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)."}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Incidence and severity of AEs graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- Part 1 – Monotherapy and Combination Dose Escalation (DE): Incidence and severity of dose-limiting toxicities (DLTs) in DLT-evaluable patients during Cycle 1","definition_or_measurement_approach":"Incidence and severity of dose-limiting toxicities assessed in DLT-evaluable patients during Cycle 1."}
• {"endpoint_text":"- Part 2 – Dose Optimization (OPT): AML: per ELN 2022 criteria CR rate","definition_or_measurement_approach":"Complete response (CR) rate in AML measured according to European LeukemiaNet (ELN) 2022 criteria."}
• {"endpoint_text":"- Part 2 – Dose Optimization (OPT): HR-MDS: per IWG 2023 criteria CR rate, defined as CR + CR equivalent","definition_or_measurement_approach":"CR rate in high-risk MDS per International Working Group (IWG) 2023 criteria, defined as CR + CR equivalent."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"AML responses and related measures assessed per ELN 2022 criteria; includes CR, composite CR, MRD-negative composite CR, ORR, duration of response, time to CR(s), transfusion independence and duration."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"HR-MDS responses assessed per IWG 2023 criteria; includes CR, ORR, duration of response, time to CR, transfusion independence and duration."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Frequency of transition to allogeneic HSCT, early death rate, EFS and OS measured using standard clinical definitions (events and survival time)."}
• {"endpoint_text":"- 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])","definition_or_measurement_approach":"Noncompartmental pharmacokinetic analysis of eganelisib including AUC, Cmax, Tmax, t1/2."}
• {"endpoint_text":"- 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])","definition_or_measurement_approach":"Noncompartmental PK analysis of cytarabine including Cmax, Tmax, AUC, and where possible t1/2, Vd, CL."}
• {"endpoint_text":"- Part 2 – Dose Optimization (OPT): Incidence and severity of AEs, graded according to the NCI CTCAE, Version 5.0","definition_or_measurement_approach":"Incidence and severity of adverse events graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"AML efficacy endpoints per ELN 2022 criteria including composite CRs, ORR, durations and transfusion independence."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"HR-MDS efficacy endpoints per IWG 2023 criteria including ORR, durations, time to CR and transfusion independence."}
• {"endpoint_text":"- Part 2 Dose Optimization (OPT): Both AML and HR-MDS; Frequency of transition to allogeneic HSCT; Early death rate; EFS; OS","definition_or_measurement_approach":"Frequency of transition to allogeneic HSCT, early death rate, event-free survival, overall survival measured by standard clinical endpoints."}

Spain

Earliest CTIS Part Ii Submission Date

19-11-2024

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

426

Number Of Sites

2

Number Of Participants

19

Primary sponsor

Full Name

Stelexis Biosciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Accovion S.L.

Responsibilities

CRO-Project Management

Name

Clinipace Inc.

Third parties

• {"country":"United States","full_name":"Keystone Bioanalytical Inc.","duties_or_roles":"PK Testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clinipace Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"IP Distribution and Labelling; Primary packaging","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"IP Distribution and Labelling","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Discovery Life Sciences LLC","duties_or_roles":"Biomarkers Analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Mlm Medical Labs LLC","duties_or_roles":"Central Lab","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Discovery Life Sciences LLC (Newtown address)","duties_or_roles":"Biomarkers Analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Tradecraft Clinical Research LLC","duties_or_roles":"Statistical Programming","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Accovion S.L.","duties_or_roles":"CRO-Project Management","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement (Spain)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Stability","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Welocalize Inc.","duties_or_roles":"Translation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Hematologics Inc.","duties_or_roles":"Biomarkers Analysis; Bone Marrow aspirate/biopsy samples","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Catalent San Diego Inc.","duties_or_roles":"Drug Product Manufacturing; Release testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"SGS North America Inc.","duties_or_roles":"Release testing of the product","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"IXRS","organisation_type":"Pharmaceutical company"}