First-in-human Trial of EGL-001 in Patients with Selected Advanced And/or Metastatic Solid Tumors

First-in-human Phase 1/2 Trial of EGL-001 in Adult Patients with Selected Advanced And/or Metastatic Solid Tumors

This multicenter, open-label, first-in-human, Phase 1/2 study consists of a Part 1 (Phase 1) open-label dose escalation of EGL-001 administered as a single agent and in combination with an anti-PD(L)-1 treatment, followed by a Part 2 (Phase 2) open-label dose expansion of EGL-001 administered at the RP2D in patients with recurrent and/or metastatic solid tumors as monotherapy and/or combination therapy with anti-PD(L)-1.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: EGL-001

Detailed Description

In approximately 4 centers in France and 4 centers in Spain, 30 to 50 patients will be included in the dose escalation Part 1 of the trial. Number of participating countries and sites as well as patients will be defined based on Part 1 for Part 2 dose expansion phase.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pejvack Motlagh, MD; Phone Number: 33660462343; Email: contact@egle-tx.com

Study Locations

• France
  • Dijon, France
    • Not yet recruiting
    • Centr Georges Francois Leclerc
    • Contact: Alice HERVIEU, MD; Phone Number: +33380737506; Email: ahervieu@cgfl.fr
  • Montpellier, France
    • Recruiting
    • Institut Régional du Cancer de Montpellier
    • Contact: Diego TOSI, MD; Phone Number: +33467612304; Email: diego.tosi@icm.unicancer.fr
  • Paris, France
    • Recruiting
    • Institut Curie
    • Contact: Christophe LE TOURNEAU, MD; Phone Number: +33144324086; Email: christophe.letourneau@curie.fr
  • Paris, France
    • Not yet recruiting
    • Institut Gustave Roussy
    • Contact: Aurélien MARABELLE, MD; Phone Number: +33142115592; Email: aurelien.marabelle@gustaveroussy.fr
• Spain
  • Barcelona, Spain
    • Not yet recruiting
    • Hospital Universitari Vall d Hebron
    • Contact: Elena GARRALDA CABANAS, MD; Phone Number: +34932746085; Email: egarralda@vhio.net
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario Fundación Jimenez Díaz
    • Contact: Victor MORENO GARCIA, MD; Phone Number: +34915504800; Email: victor.moreno@startmadrid.com
  • Pamplona, Spain
    • Not yet recruiting
    • Clinica Universidad de Navarra
    • Contact: Ana LANDA MAGDALENA, MD; Phone Number: +34948255400; Email: alandam@unav.es
  • Valencia, Spain
    • Recruiting
    • Hospital Clinico Universitario de Valencia
    • Contact: Valentina GAMBARDELLA, MD; Phone Number: +34691135106; Email: Valen.gambardella@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed written informed consent
2. Female or male patients, aged at least 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
4. Life expectancy of at least 3 months as assessed by the investigator
5. 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
6. Patients who have been treated with an ICI treatment as monotherapy or in combination as SoC
7. Have recovered from previous treatment
8. At least 1 measurable lesion according to RECIST Version 1.1
9. Adequate hematological, hepatic, and renal functions
10. Negative blood pregnancy test at screening for women of childbearing potential

11. 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
12. Must agree to abstain from donating blood while taking study drug and for 3 months following discontinuation of study treatment
13. Able to understand the character and individual consequences of clinical trial

Exclusion Criteria:

1. Patients with central nervous system metastases and/or leptomeningeal carcinomatosis with some exceptions
2. Patients with active or a documented history of autoimmune disease, immune deficiency or syndrome that required systemic corticoids (except the allowed dose) or immunosuppressive medications
3. 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 was discontinued from that treatment due to toxicity
4. 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
5. Patients with history of or current interstitial lung disease or fibrosis, and patients with pneumonitis
6. Other active malignancy requiring active intervention
7. 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
8. Patient with any organ transplantation, including allogeneic stem cell transplantation
9. Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma
10. Any known allergy or severe reaction to any component of anti-CTLA-4 or anti-PD(L)-1 drug product
11. Significant chronic or acute infections requiring systemic therapy including SARS-CoV-2 (COVID-19) PCR positive testing
12. Clinically significant active cardiovascular disease
13. 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
14. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy EGL-001 Dose Level 1; EGL-001 Dose Level 1	Drug: EGL-001; IV administration
Experimental: Monotherapy EGL-001 Dose Level 2; EGL-001 Dose Level 2	Drug: EGL-001; IV administration
Experimental: Monotherapy EGL-001 Dose Level 3; EGL-001 Dose Level 3	Drug: EGL-001; IV administration
Experimental: Monotherapy EGL-001 Dose Level 4; EGL-001 Dose Level 4	Drug: EGL-001; IV administration
Experimental: Monotherapy EGL-001 Dose Level 5; EGL-001 Dose Level 5	Drug: EGL-001; IV administration
Experimental: Monotherapy EGL-001 Dose Level 6; EGL-001 Dose Level 6	Drug: EGL-001; IV administration
Experimental: Monotherapy EGL-001 Dose Level 7; EGL-001 Dose Level 7	Drug: EGL-001; IV administration
Experimental: Combination therapy with EGL-001 dose Level x; EGL-001 Dose Level x in combination with anti-PDL1	Drug: EGL-001; IV administration
Experimental: Combination therapy with EGL-001 dose Level y; EGL-001 Dose Level y in combination with anti-PDL1	Drug: EGL-001; IV administration
Experimental: Combination therapy with EGL-001 dose Level z; EGL-001 Dose Level z in combination with anti-PDL1	Drug: EGL-001; IV administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety, tolerability, dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) leading to the recommended Phase 2 doses (RP2Ds)	DLTs occurrence per dose level of EGL-001 during the DLT period (number)	Day 1 up to 90 days after last dose
To evaluate the safety, tolerability, dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) leading to the recommended Phase 2 doses (RP2Ds)	Proportion of patients with adverse events (AEs) (%)	Day 1 up to 90 days after last dose
To evaluate the safety, tolerability, dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) leading to the recommended Phase 2 doses (RP2Ds)	Proportion of patients with treatment-emergent AEs (TEAEs) (%)	Day 1 up to 90 days after last dose
To evaluate the safety, tolerability, dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) leading to the recommended Phase 2 doses (RP2Ds)	Proportion of patients with serious AEs (SAEs) (%)	Day 1 up to 90 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the preliminary antitumor efficacy (according to RECIST v1.1)	ORR: the proportion of patients with complete response (CR) or partial response PR), based on local evaluations using RECIST Version 1.1. (%)	From Dose 1 to to the date of first documented tumor progression or death due to any cause, whichever occurs first.
To evaluate the preliminary antitumor efficacy (according to RECIST v1.1)	Disease control rate (DCR): the proportion of patients with CR, PR, or stable disease (SD), and assessment of DCR at 6 months (%)	From Dose 1 to to the date of first documented tumor progression or death due to any cause, whichever occurs first.
To evaluate the preliminary antitumor efficacy (according to RECIST v1.1)	Duration of overall response (DoR): applies only to patients with CR or PR. The start date is the date of first documented response (CR or PR), and the end date is the date of first documented disease progression or the date of death due to underlying cancer (months)	From Dose 1 to to the date of first documented tumor progression or death due to any cause, whichever occurs first.
To evaluate the preliminary antitumor efficacy (according to RECIST v1.1)	PFS: time from the date of first study treatment administration to the date of first documented tumor progression or death due to any cause, whichever occurs first (months)	From Dose 1 to to the date of first documented tumor progression or death due to any cause, whichever occurs first.
To evaluate the preliminary antitumor efficacy (according to RECIST v1.1)	OS: time from the date of first study treatment administration to the date of death due to any cause. If a patient is not known to have died at the cut-off date for analysis, survival will be censored at the date of last contact (months)	From Dose 1 to to the date of first documented tumor progression or death due to any cause, whichever occurs first.

Collaborators and Investigators

• Sponsor: Egle Therapeutics
• Investigators: Study Director: Pejvack Motlagh, MD, Egle Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2024
• Primary Completion (Estimated): January 23, 2027
• Study Completion (Estimated): January 23, 2027

Study Registration Dates

• First Submitted: September 26, 2024
• First Submitted That Met QC Criteria: September 30, 2024
• First Posted (Actual): October 2, 2024

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: EGL-121; 2024-512921-10-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Consequences (RA approval, data protection, operations for datamanagement, impact on IP, on budget…) for sharing IPD are not understood by Egle-Tx. This will be done at a later stage if necessary.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No