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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Egle Therapeutics

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

27 Sep 2024 → ongoing

Decision date (initial)

2024-09-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512921-10-00

WHO UTN

U1111-1307-8455

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Safety

The Primary Objectives for the Part 1 (dose escalation) are to evaluate the safety, tolerability, and dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) during weekly administration of EGL-001 leading to the recommended selected doses of EGL-001 monotherapy or in combination with pembrolizumab in adult patients with selected advanced/metastatic solid tumors and to evaluate the safety and tolerability of EGL-001 monotherapy administration in a 3-weekly (Q3W) schedule.

The Primary Objective for the Part 2 (dose expansion) is to evaluate preliminary efficacy as defined by objective response rate (ORR) for the selected doses of EGL-001 monotherapy and/or in combination with pembrolizumab in adult patients with selected advanced/metastatic solid tumors.

Secondary objectives 2

1. The Secondary Objective for the Part 1 (dose escalation) is to evaluate the preliminary antitumor efficacy of EGL-001 monotherapy and/or in combination with pembrolizumab.
2. The Secondary Objective for the Part 2 (dose expansion) is to further evaluate the safety, tolerability, and efficacy of selected doses of EGL-001 monotherapy and/or in combination with pembrolizumab.

Conditions and MedDRA coding

Advanced and/or Metastatic Solid Tumors

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products

Plan to share IPD

No

IPD plan description

Consequences (e.g. RA approval, data protection, operations for data management, impact on IP, on budget) for sharing IPD are being discussed by Egle and plan to share IPD may be updated at a later stage if necessary.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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

Exclusion criteria 14

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Dose-limiting toxicities (DLTs) when patients are receiving weekly administration of EGL-001 and proportion of patients with adverse events (AEs), treatment-emergent AEs (TEAEs), and serious AEs (SAEs) between the first dose of study drug and up to 90 days after the last dose of study drug.
2. Proportion of patients with complete response (CR) or partial response (PR).

Secondary endpoints 2

1. Efficacy assessment based on Overall response rate (ORR), Disease control rate (DCR), Duration of overall response (DoR), Progression-free survival (PFS), Overall survival (OS).
2. The proportion of patients with adverse events (AEs), treatment-emergent adverse events (TEAEs), and Serious adverse Events (SAEs) between the first dose of study drug and up to 90 days after the last dose of study drug.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Egle Therapeutics

Sponsor organisation

Egle Therapeutics

Address

5 Rue Gardenat Lapostol

City

Suresnes

Postcode

92150

Country

France

Scientific contact point

Organisation

Egle Therapeutics

Contact name

Kenji Hashimoto

Public contact point

Organisation

Egle Therapeutics

Contact name

Kenji Hashimoto

Third parties 6

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications