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

Official title

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

Overview

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.

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.

Interventions

• Drug EGL-001
  IV administration

Primary outcome measures

• To evaluate the safety, tolerability, dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) leading to the recommended Phase 2 doses (RP2Ds) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: Day 1 up to 90 days after last dose]

Secondary outcome measures (5)

• To evaluate the preliminary antitumor efficacy (according to RECIST v1.1) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: From Dose 1 to to the date of first documented tumor progression or death due to any cause, whichever occurs first.]

Eligibility 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 a 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 was 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

France · 4 centers

• Centr Georges Francois Leclerc — Dijon
• Institut Regional Du Cancer De Montpellier — Montpellier
• Institut Curie — Paris
• Institut Gustave Roussy — Paris

Spain · 4 centers

• Hospital Universitari Vall D Hebron — Barcelona
• Hospital Universitario Fundacion Jimenez Diaz — Madrid
• Clinica Universidad De Navarra — Pamplona
• Hospital Clinico Universitario De Valencia — Valencia

Identifiers

NCT: NCT06622486 · EGL-121 · 2024-512921-10-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗