Phase 1/2 Evaluation of EGL-001 Monotherapy and Combination with Anti-PD(L)-1 in Advanced/Metastatic Solid Tumors
- Trial ID
- 2024-512921-10-00
- Protocol
- EGL-121
- Sponsor
- Egle Therapeutics
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this first-in-human Phase 1/2 trial is to evaluate the **safety**, tolerability, and dose-limiting toxicities (DLTs) of EGL-001, as well as to determine the maximum tolerated dose (MTD) in adult patients with selected advanced and/or metastatic solid tumors during the dose escalation phase. Additionally, the trial aims to assess the preliminary efficacy, defined by the objective response rate (ORR), for the recommended Phase 2 dose (RP2D) of EGL-001 monotherapy and/or in combination with an anti-PD(L)-1 during the dose expansion phase. These objectives are clinically relevant as they provide critical information on the safety profile and potential therapeutic efficacy of EGL-001, which is essential for the development of new treatment options for patients with advanced solid tumors.
Secondary objectives include: - For Part 1 (dose escalation), evaluating the preliminary antitumor efficacy of EGL-001 monotherapy and/or in combination with an anti-PD(L)-1. - For Part 2 (dose expansion), further evaluating the safety, tolerability, and efficacy of EGL-001. These secondary objectives aim to provide additional insights into the therapeutic potential and safety of EGL-001, supporting its further clinical development.
Participants
The clinical trial involves **adult patients** with **advanced and/or metastatic solid tumors**. The study population includes both male and female participants aged 18 years and older. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population was selected based on their previous treatment history, specifically those who have been treated with standard of care (SoC) therapies and are no longer eligible for other treatments. Additionally, participants must have been treated with immune checkpoint inhibitors (ICI) either as monotherapy or in combination as SoC and have recovered from previous treatments. They must have at least one measurable lesion according to RECIST Version 1.1 and possess adequate hematological, hepatic, and renal functions. The sponsor has not provided the total number of participants involved in the study. Lifestyle considerations such as diet and physical activity are not specified, but participants must agree to use highly effective contraception methods and abstain from donating blood during and after the study period. The trial includes a vulnerable population, and all participants must have a life expectancy of at least three months as assessed by the investigator.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, and **controlled** study designed to evaluate the safety, tolerability, and efficacy of the investigational drug EGL-001 in adult patients with **advanced and/or metastatic solid tumors**. The trial is structured in two parts: Part 1 focuses on dose escalation to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs), while Part 2 aims to assess the preliminary efficacy of EGL-001 as monotherapy or in combination with an anti-PD(L)-1 agent. The trial is expected to span approximately three years, with an estimated end date in January 2027.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance status, and previous treatment history. Following successful screening, participants will be randomized to receive EGL-001 via **intravenous infusion**. Regular follow-up visits will be scheduled to monitor safety, adverse events, and treatment response, with assessments including imaging studies and laboratory tests. The end-of-study visit will occur 90 days after the last dose of the study drug, during which final evaluations will be conducted.
The expected length of participant involvement is up to 52 weeks, depending on individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include the occurrence of unacceptable adverse events, disease progression, or withdrawal of consent by the participant. The primary endpoints of the trial include the incidence of DLTs and the proportion of patients experiencing adverse events, while secondary endpoints focus on overall response rate, disease control rate, and survival outcomes.
Treatment
The clinical trial involves the administration of **EGL-001**, an experimental medication developed by Egle Therapeutics. **EGL-001** is formulated as a **solution for infusion** and is intended for **intravenous use**. The active substance in **EGL-001** is a protein of other origin, specifically designed for the treatment of selected advanced and/or metastatic solid tumors. The dosing regimen for **EGL-001** is based on a milligram per kilogram (**mg/kg**) body weight basis, although the specific dosage and maximum daily dose are not predetermined, allowing for dose escalation to determine the maximum tolerated dose (MTD). The maximum treatment period for **EGL-001** is set at 52 weeks.
In this trial, **EGL-001** is administered as a monotherapy and may also be evaluated in combination with an anti-PD(L)-1 therapy. The trial is structured in two parts: Part 1 focuses on dose escalation to assess safety, tolerability, and dose-limiting toxicities, while Part 2 aims to evaluate the preliminary efficacy of the recommended Phase 2 dose (RP2D) based on objective response rate (ORR). No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this study. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the evaluation of the **objective response rate (ORR)** for the recommended Phase 2 dose (RP2D) of EGL-001, administered as monotherapy or in combination with an anti-PD(L)-1, in adult patients with selected advanced or metastatic solid tumors. The primary endpoints include the proportion of patients achieving a complete response (CR) or partial response (PR). Secondary efficacy assessments will include the overall response rate (ORR), disease control rate (DCR), duration of overall response (DoR), progression-free survival (PFS), and overall survival (OS).
The collection and analysis of these efficacy parameters will be conducted at specified intervals throughout the trial. The trial will utilize validated criteria, such as RECIST Version 1.1, to measure and categorize tumor responses. The schedule for efficacy assessments will align with the trial's protocol, ensuring systematic data collection and analysis. The trial is designed to provide a comprehensive evaluation of EGL-001's efficacy in the specified patient population, contributing to the understanding of its therapeutic potential in advanced and metastatic solid tumors.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed written informed consent.
- Female or male patients, aged at least 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Life expectancy of at least 3 months as assessed by the investigator.
- Patients with confirmed locally advanced, unresectable, or metastatic solid tumors who have been previously treated with SoC and are no longer eligible for other therapies.
- Patients who have been treated with an ICI treatment as monotherapy or in combination as SoC.
- Have recovered from previous treatment.
- At least 1 measurable lesion according to RECIST Version 1.1.
- Adequate hematological, hepatic, and renal functions.
- Negative blood pregnancy test at screening for women of childbearing potential.
- Highly effective contraception during the study period and for 6 months after the last study treatment administration for WOCBP, and for male patients who are sexually active with WOCBP. Highly effective contraception methods are defined as: • Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectable, implants, intrauterine devices such as Mirena and nonhormonal intrauterine devices such as ParaGard for WOCBP patients or male patients’ WOCBP partners • Tubal ligation • Vasectomy; In addition to highly effective contraception, participating male patients: • Must use a condom during the study period and for 3 months after the last study treatment administration when engaging in any activity that allows for exposure to ejaculate • Must refrain from donating sperm.
- Must agree to abstain from donating blood while taking study drug and for 3 months following discontinuation of study treatment.
- Able to understand the character and individual consequences of clinical trial.
Exclusion Criteria
- Patients with central nervous system metastases and/or leptomeningeal carcinomatosis with some exceptions.
- Patients with active or documented history of autoimmune disease, immune deficiency or syndrome that required systemic corticoids (except the allowed dose) or immunosuppressive medications.
- Patients who received a previous ICI (like anti-PD(L)-1 or an agent directed to another stimulatory or co-inhibitory T-cell receptor) and were discontinued from that treatment due to toxicity.
- Patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs for a period of at least 4 weeks and whose treatment was not stopped 2 weeks prior to the first study treatment, with exceptions. Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
- Patients with history of or current interstitial lung disease or fibrosis, and patients with pneumonitis.
- Other active malignancy requiring active intervention.
- Patients with previous malignancies other than the target malignancy to be investigated in this trial, unless a complete remission was achieved and no additional therapy is required during the study period.
- Patient with any organ transplantation, including allogeneic stem cell transplantation.
- Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma.
- Any known allergy or severe reaction to any component of anti-CTLA-4 or anti-PD(L)-1 drug product.
- Significant chronic or acute infections requiring systemic therapy including SARS-CoV-2 (COVID-19) PCR positive testing.
- Clinically significant active cardiovascular disease.
- Any other medical conditions or psychological disorders that would increase the safety risk to the patient or interfere with participation of the patient or the evaluation of the clinical study in the opinion of the investigator.
- Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 02 Oct 2024 | 31 |
 Spain | Recruiting | 02 Oct 2024 | 31 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
EGL-001 | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 0 | 52 | PRD11321696 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 52 | PRD4323105 |