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EGANELISIB

EGANELISIB (also known as IPI-549) is an innovative drug currently being investigated in multiple clinical trials for various types of cancer. As a first-in-class, oral immuno-oncology medication, EGANELISIB works by targeting immune-suppressive tumor-associated myeloid cells through selective inhibition of phosphoinositide-3-kinase (PI3K)-gamma. This mechanism helps to overcome immune suppression in the tumor microenvironment, potentially making cancer treatments more effective. The drug is being studied both as a monotherapy and in combination with other cancer treatments for conditions including acute myeloid leukemia, solid tumors, triple-negative breast cancer, renal cell carcinoma, and urothelial carcinoma. These trials aim to evaluate the safety, tolerability, and efficacy of EGANELISIB in patients with advanced cancers who need new treatment options.

# Eganelisib: A Promising Treatment for Various Cancers Table of Contents – [What is Eganelisib?](#what-is-eganelisib) – [How Eganelisib Works](#how-eganelisib-works) – [Medical Conditions Treated](#medical-conditions-treated) – [Eganelisib in Combination Therapies](#eganelisib-in-combination-therapies) – [Clinical Trials](#clinical-trials) – [Safety and Side Effects](#safety-and-side-effects) – [Administration](#administration) What is Eganelisib? Eganelisib (also known as IPI-549) is a first-in-class, oral medication that is being studied for the treatment of various types of cancer [1]. It belongs to a class of drugs that selectively inhibits an enzyme called phosphoinositide-3-kinase gamma (PI3K-gamma) [4]. Eganelisib is currently being investigated in multiple clinical trials to evaluate its effectiveness and safety, both as a standalone treatment (monotherapy) and in combination with other cancer medications [2]. How Eganelisib Works Eganelisib works by targeting immune-suppressive tumor-associated myeloid cells through selective inhibition of PI3K-gamma [4]. In simpler terms, the drug helps to reprogram certain immune cells (macrophages) in the tumor microenvironment. This reprogramming can potentially help your immune system better recognize and attack cancer cells. By targeting the PI3K-gamma pathway, eganelisib aims to overcome one of the mechanisms by which cancer cells evade the immune system [2]. Medical Conditions Treated Based on ongoing clinical trials, eganelisib is being investigated for the treatment of several types of cancer:
  • Blood Cancers:
    • Acute Myeloid Leukemia (AML) – a type of cancer that affects the blood and bone marrow [1]
    • Higher-risk Myelodysplastic Syndromes (HR-MDS) – a group of disorders characterized by poorly formed or dysfunctional blood cells [1]
  • Solid Tumors:
    • Advanced Urothelial Carcinoma (bladder cancer) [3]
    • Triple-Negative Breast Cancer (TNBC) [4]
    • Renal Cell Carcinoma (kidney cancer) [4]
    • Non-small Cell Lung Cancer [2]
    • Melanoma (skin cancer) [2]
    • Squamous Cell Cancer of the Head and Neck [2]
    • Adrenocortical Carcinoma [2]
    • Mesothelioma [2]
The drug is particularly being studied in patients whose cancer has relapsed (come back) or is refractory (not responding to previous treatments) [1]. Eganelisib in Combination Therapies Eganelisib is being studied both as a standalone treatment and in combination with other cancer medications. Some of the combination therapies include: Eganelisib + Cytarabine: For patients with relapsed or refractory acute myeloid leukemia or higher-risk myelodysplastic syndromes [1] Eganelisib + Nivolumab (Opdivo): For patients with various advanced solid tumors, including urothelial carcinoma [2] [3] Eganelisib + Atezolizumab (Tecentriq) + nab-paclitaxel (Abraxane): For patients with triple-negative breast cancer [4] Eganelisib + Atezolizumab (Tecentriq) + Bevacizumab (Avastin): For patients with renal cell carcinoma [4] These combinations are designed to potentially enhance the effectiveness of each drug and provide better outcomes for patients [4]. Clinical Trials Several clinical trials are currently underway to evaluate eganelisib:
  • NCT06533761: A Phase 1b study evaluating the safety and tolerability of eganelisib as monotherapy and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia or higher-risk myelodysplastic syndromes [1]
  • NCT02637531 (IPI-549-01): A Phase 1/1b dose-escalation study to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of eganelisib monotherapy and in combination with nivolumab in subjects with advanced solid tumors [2]
  • NCT03980041 (MARIO-275): A Phase 2 study to evaluate the efficacy and safety of nivolumab administered in combination with eganelisib compared to nivolumab monotherapy in the treatment of patients with immune therapy-naïve, advanced urothelial carcinoma [3]
  • NCT03961698 (MARIO-3): A Phase 2 study to evaluate efficacy and safety of eganelisib administered in combination with front-line treatment regimens in patients with locally advanced and/or metastatic triple-negative breast cancer or renal cell carcinoma [4]
These trials are examining various aspects of the drug, including:
  • Finding the right dose (dose-escalation and dose-optimization) [1]
  • Understanding how the drug moves through the body (pharmacokinetics) [2]
  • Studying how the drug affects the body (pharmacodynamics) [2]
  • Measuring the drug’s effectiveness against cancer (anti-tumor efficacy) [1]
  • Assessing safety and side effects [3]
Safety and Side Effects As with any medication under investigation, the safety profile and potential side effects of eganelisib are being carefully studied in clinical trials. Common measures being tracked include: Incidence and severity of adverse events (AEs) [1] Dose-limiting toxicities (DLTs) [1] Changes in vital signs (pulse rate, temperature, respiration rate, blood pressure) [3] [4] Changes in electrocardiograms (ECGs) [3] [4] Changes in laboratory values, including thyroid function tests [3] The trials are designed to identify any safety concerns and determine the most appropriate dosage for patients [1]. Administration Eganelisib is an oral medication, typically administered as a daily dose in capsule form [2] [4]. The specific dosage can vary depending on the clinical trial and whether it’s being used alone or in combination with other treatments:
  • When used as monotherapy, doses are being studied in a range, with some trials examining once-daily (QD) or twice-daily (BID) administration [2]
  • In combination therapy studies, dosages of 20mg/day, 30mg/day, or 40mg/day are being evaluated [4]
  • Treatment is typically organized in cycles, often 28-day cycles for monotherapy and combination therapy with various drugs [3]
The optimal dosage and administration schedule will be determined based on the results of ongoing clinical trials [1].
Clinical Trial Cancer Types Study Design Treatment Approach Key Outcomes Measured
NCT06533761 Relapsed/Refractory Acute Myeloid Leukemia (AML) or Higher-Risk Myelodysplastic Syndromes (HR-MDS) Phase 1b, open-label, multicenter study with dose escalation and optimization EGANELISIB as monotherapy and in combination with cytarabine Safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor efficacy
NCT02637531 Advanced solid tumors including NSCLC, melanoma, head and neck cancer, triple-negative breast cancer, adrenocortical carcinoma, and mesothelioma Phase 1/1b first-in-human, dose-escalation study with multiple parts EGANELISIB (IPI-549) as monotherapy and in combination with nivolumab Safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity
NCT03980041 Advanced urothelial carcinoma (bladder cancer) Phase 2, multicenter, randomized, double-blind, active-control study EGANELISIB (IPI-549) in combination with nivolumab compared to nivolumab monotherapy Objective response rate, time to response, duration of response, progression-free survival
NCT03961698 Locally advanced and/or metastatic triple-negative breast cancer (TNBC) and renal cell carcinoma (RCC) Phase 2, multi-arm, multicenter, open-label study EGANELISIB with atezolizumab and nab-paclitaxel for TNBC; EGANELISIB with atezolizumab and bevacizumab for RCC Complete response rate, safety, objective response rate, time to response, duration of response, progression-free survival

FAQ

  • What is EGANELISIB and how does it work? EGANELISIB (also known as IPI-549) is an oral medication that selectively inhibits phosphoinositide-3-kinase (PI3K)-gamma. This enzyme plays a key role in immune-suppressive tumor-associated myeloid cells. By blocking PI3K-gamma, EGANELISIB helps reprogram these cells, potentially turning the tumor microenvironment from immunosuppressive to immunostimulatory. This mechanism may enhance the body's immune response against cancer cells, especially when combined with other treatments.
  • What types of cancer is EGANELISIB being tested for? EGANELISIB is currently being evaluated in clinical trials for multiple cancer types, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), advanced solid tumors, triple-negative breast cancer (TNBC), renal cell carcinoma (RCC), urothelial carcinoma, non-small cell lung cancer (NSCLC), melanoma, and head and neck cancer. The trials explore its use both as a single agent and in combination with other cancer therapies.
  • How is EGANELISIB administered in clinical trials? EGANELISIB is administered orally as a daily dose in most clinical trials. The dosing regimens vary by trial, with some studies testing different dose levels (ranging from 20mg to 40mg daily) to determine the optimal dose. Treatment typically continues in cycles (often 28-day cycles) until disease progression, unacceptable toxicity, or other discontinuation criteria are met.
  • What other drugs is EGANELISIB being combined with in trials? EGANELISIB is being studied in combination with several other cancer treatments. These include immune checkpoint inhibitors like nivolumab (OPDIVO) and atezolizumab (Tecentriq), chemotherapy agents such as cytarabine and nab-paclitaxel (Abraxane), and targeted therapies like bevacizumab (Avastin). These combinations are being tested to determine if EGANELISIB can enhance the effectiveness of these established cancer treatments.
  • What are researchers measuring in these EGANELISIB clinical trials? Researchers are evaluating several important outcomes in EGANELISIB trials. Primary measures include safety and tolerability (monitoring side effects and dose-limiting toxicities), as well as effectiveness measures like objective response rate (the percentage of patients whose tumors shrink), complete response rate, duration of response, and progression-free survival. They're also studying how the drug moves through the body (pharmacokinetics), how it affects the body (pharmacodynamics), and its impact on specific biomarkers that might predict which patients will benefit most from treatment.

Ongoing Clinical Trials on EGANELISIB

  • Study on the Safety of Eganelisib Alone and with Cytarabine for Patients with Relapsed or Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndromes

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Spain

Glossary

  • Acute Myeloid Leukemia (AML): A type of cancer that affects the blood and bone marrow, characterized by rapid growth of abnormal white blood cells that build up in the bone marrow and interfere with normal blood cell production.
  • Myelodysplastic Syndromes (MDS): A group of disorders caused by poorly formed blood cells or ones that don't work properly, often referred to as 'higher-risk' when they have a greater chance of progressing to acute myeloid leukemia.
  • Phosphoinositide-3-kinase (PI3K)-gamma: An enzyme mainly found in immune cells that plays a key role in the function of myeloid cells in the tumor environment. EGANELISIB works by specifically blocking this enzyme.
  • Immunotherapy: A type of cancer treatment that helps the body's immune system fight cancer. EGANELISIB is considered an immuno-oncology agent because it targets immune cells to enhance anti-tumor responses.
  • Triple-Negative Breast Cancer (TNBC): A type of breast cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein, making it more difficult to treat than other types of breast cancer.
  • Renal Cell Carcinoma (RCC): The most common type of kidney cancer in adults, which begins in the cells that line the small tubes in the kidney that filter blood and remove waste.
  • Urothelial Carcinoma: The most common type of bladder cancer, which starts in the urothelial cells that line the inside of the bladder and other parts of the urinary tract.
  • Objective Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment. It includes both complete responses (cancer disappears completely) and partial responses (cancer shrinks significantly).
  • Progression-Free Survival (PFS): The length of time during and after treatment that a patient lives with cancer without it getting worse.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including how it is absorbed, distributed, metabolized, and excreted.
  • Pharmacodynamics (PD): The study of how a drug affects the body, including its biochemical and physiological effects.
  • Dose-Limiting Toxicity (DLT): Side effects that are severe enough to prevent increasing the dose of a drug during a clinical trial.
  • Checkpoint Inhibitor: A type of drug that blocks certain proteins made by immune system cells, such as PD-1 and CTLA-4, which help keep immune responses in check. Blocking these proteins allows immune cells to more effectively kill cancer cells.
  • Nivolumab: An immune checkpoint inhibitor that targets the PD-1 pathway and is often used in combination with EGANELISIB in clinical trials.
  • Cytarabine: A chemotherapy drug commonly used to treat certain types of leukemia and lymphomas. It works by interfering with DNA synthesis, which prevents cancer cells from growing and dividing.
  • Duration of Response (DOR): The time from when a tumor starts responding to treatment until it begins to grow again.
  • RECIST v1.1: Response Evaluation Criteria in Solid Tumors, version 1.1 – a standardized set of rules used to measure how well a cancer patient responds to treatment, based on whether tumors shrink, stay the same, or get bigger.
  • Monotherapy: Treatment using a single drug, as opposed to combination therapy which uses multiple drugs.
  • Phase 1 Clinical Trial: The first stage of testing in humans, primarily focused on evaluating safety, determining safe dosage ranges, and identifying side effects.
  • Phase 2 Clinical Trial: The second stage of testing, which provides preliminary data on whether a drug works in people who have a certain disease or condition. These trials also continue to study safety.

References

  1. https://clinicaltrials.eu/trial/study-on-the-safety-of-eganelisib-alone-and-with-cytarabine-for-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-or-higher-risk-myelodysplastic-syndromes/
  2. https://clinicaltrials.gov/study/NCT02637531
  3. https://clinicaltrials.gov/study/NCT03980041
  4. https://clinicaltrials.gov/study/NCT03961698