Assessing PI3K Gamma Inhibition With Azacitidine, Venetoclax and Eganelisib in Patients With Acute Myeloid Leukemia

NCT07439211 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DFCI 25-820
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

This study is to evaluate the safety and preliminary efficacy of adding the PI3K-gamma inhibitor, eganelisib, to a standard of care treatment option with combination venetoclax and azacitidine in participants with acute myeloid leukemia (AML). The names of the study drugs involved in this research study are:

• Venetoclax (a type of BCL-2 inhibitor)
• Azacitidine (a type of Demethylating Agent)
• Eganelisib (a type of PI3K-gamma inhibitor)

Conditions

Leukemia, Myeloid; Leukemia; Acute Myeloid Leukemia; Refractory Leukemia

Keywords

Leukemia, Myeloid; Leukemia; Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Relapsed Acute Myeloid Leukemia; AML

Outcome Measures

Primary Outcomes (2)

• Eganelisib Recommended Phase 2 Dose (RP2D)

  The eganelisib (daily) RP2D in combination with azacitidine 75 mg/m\^2/day on days 1-7 and venetoclax 400 mg daily (28 days) is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The RP2D is based on the Bayesian optimal interval design (BOIN). The RP2D may also be based on available pharmacokinetic (PK) and pharmacodynamic (PD) data.

  1 cycle=28 days

• Recommended Phase 2 Dose (RP2D)

  Number of Participants experiencing protocol-defined DLT

  1 cycle=28 days

Secondary Outcomes (9)

• Treatment-Related Grade 3-4 Adverse Event (AE) Rate

  through study completion, an average of 2 years

• Eganelisib Feasibility Rate

  First 28 days

• Eganelisib Area Under the Plasma Concentration versus Time Curve (AUC)

  Up to 4 months

• Complete Remission (CR) Rate

  Up to 4 months

• CR with Partial Hematologic Recovery (CRh) Rate

  Up to 4 months

Study Arms (2)

Dose-Escalation Eganelisib

EXPERIMENTAL

Dose-Escalation with triplet azacitidine D1-7, venetoclax D1-28 and eganelisib D1-28 (dose-escalated) * Baseline visit * Treatment in 28 day cycles * End of treatment visit * Follow up every 4 months for up to 1 year after end of treatment (for survival).

Drug: Eganelisib; Drug: Azacitidine; Drug: Venetoclax

Dose-Expansion Eganelisib

EXPERIMENTAL

Dose-Escalation with triplet azacitidine D1-7, venetoclax D1-28 and eganelisib D1-28 (dose-expansion at MTD/RP2D) * Baseline visit * Treatment in 28 day cycles * End of treatment visit * Follow up every 4 months for up to 1 year after end of treatment (for survival).

Drug: Eganelisib; Drug: Azacitidine; Drug: Venetoclax

Interventions

Eganelisib DRUG

PI3K-gamma inhibitor, capsule taken orally per protocol.

Also known as: IPI-549

Dose-Escalation Eganelisib; Dose-Expansion Eganelisib

Azacitidine DRUG

Demethylating Agent, single use vial, via subcutaneous (under the skin) injection or intravenous (into the vein) infusion per standard of care.

Dose-Escalation Eganelisib; Dose-Expansion Eganelisib

Venetoclax DRUG

BCL-2 inhibitor, tablet taken orally per standard of care.

Also known as: C45H50ClN7O7S

Dose-Escalation Eganelisib; Dose-Expansion Eganelisib

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically confirmed AML that meets one of these categories of disease:
• Group A: Relapsed or Refractory: Subjects with relapsed or refractory AML or relapsed/refractory AML, who are not recommended for any approved targeted therapy must meet any one of the following criteria: (1) morphologic relapse (at least 5% blasts), or (2) refractory to intensive chemotherapy (at least one cycle of cytarabine and anthracycline-based intensive regimen) or at least 2 cycles of prior HMA/venetoclax-based therapy (without CR/CRh/CRi). No limit to prior lines of AML therapy. OR
• (Expansion only) Group B: Untreated AML with ELN 2022 adverse risk disease: Subjects with newly diagnosed or previously untreated AML must be ineligible for intensive chemotherapy based on Ferrara criteria (age ≥75 years or presence of co- morbidity).
• Evidence of marrow involved AML.
• Age 18-90 years. Because no dosing or adverse event data are currently available on the use of eganelisib in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group performance status ≤ 3 if 18 to 74 years of age or ECOG 0-2 if ≥ 75 years of age.
• Subjects must meet the following organ and marrow function as defined below:
• total serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) or
• ≤ 3 x ULN in case of Gilbert's disease
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x × institutional ULN
• Creatinine clearance (CrCl) ≥ 30 L/min (Cockcroft-Gault formula)
• Prior history of CNS leukemia that has been treated, asymptomatic and controlled are eligible. CNS evaluation is not required for screening if asymptomatic.
• Subjects with a prior or concurrent malignancy (other than MDS, MPN, MDS/MPN, or AML) whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Treatment must be at least 12 months from last dose of chemotherapy or immunotherapy (except no window is required for palliative radiation or supportive or hormonal therapies). Concurrent malignancy must be considered not active or requiring therapy.
• Male subjects and female subjects/women of childbearing potential (WCBP) must agree to the following: The effects of eganelisib on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. When eganelisib is being used alone, the duration of contraception after the last dose should be 3 months for both males and females of childbearing potential. When eganelisib is being used with azacitidine + venetoclax, according to the USPI for azacitidine, females of reproductive potential should use effective contraception during treatment with azacitidine and for 6 months after the last dose and males with female partners of reproductive potential should use effective contraception during treatment with azacitidine and for 3 months after the last dose. WCBP must have negative serum beta human chorionic gonadotropin test measured within 7 days prior to the first dose of eganelisib and consent to ongoing pregnancy testing during the study.
• Willingness to practice adequate sun protection (i.e. 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.

You may not qualify if:

• Prior systemic cancer therapy is allowed as long as \>14 days prior to study treatment start. Hormonal therapy may be allowed if approved by Sponsor-Investigator.
• Major surgery within 28 days prior to study treatment start.
• Allogeneic stem cell transplant within 100 days prior to study treatment start.
• Active graft-versus-host disease (GVHD) after allogeneic stem cell transplantation or chronic GVHD requiring systemic steroid administration. Topical therapies are allowed for controlled GVHD.
• Receiving systemic immunosuppressive therapy such as steroids or calcineurin inhibitors.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy with the exception of alopecia.
• Participants who are receiving any other investigational AML directed-agents for this condition.
• White blood cell count \> 25x109/L prior to first dose of study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to eganelisib, venetoclax, or azacitidine.
• Participants receiving any medications or substances within 14 days prior to first dose of study drug and for duration of the study:
• 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 (preference for moderate CYP3A inhibitors if antifungal therapy is recommended when clinically acceptable).
• P-glycoprotein (P-gp) inhibitors except for azole antifungals.
• Breast cancer resistance protein (BCRP) inhibitors.
• Administration of any of the following as of Cycle 1 Day 1 and for the study duration: Substrates with a narrow therapeutic index for P-gp, or Warfarin, phenytoin, or other substrates with a narrow therapeutic index for CYP2C8 or CYP2C9
• Pregnant women are excluded from this study because eganelisib is an agent without known fertility and developmental toxicity studies. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with eganelisib, breastfeeding should be discontinued if the mother is treated with eganelisib. These potential risks may also apply to other agents used in this study.

Sponsors & Collaborators

• Jacqueline Garcia, MD: lead
• Stelexis BioSciences, Inc.: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute

Interventions

IPI-549; Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jacqueline Garcia, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jaqueline Garcia, MD

CONTACT

617-632-6577; jacqueline_garcia@dfci.harvard.edu

Jacqueline Garcia, MD

CONTACT

617-632-6577; jacqueline_garcia@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: dose-escalation followed by expansion

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: February 27, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)