A clinical trial to investigate EO4010, a novel cancer vaccine therapy, with an immune checkpoint blocker, in patients with previously treated metastatic colorectal carcinoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Enterome

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 May 2023 → 31 May 2025

Decision date (initial)

2024-07-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Enterome SA, France

External identifiers

EU CT number

2023-509509-62-00

EudraCT number

2022-002805-90

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacogenetic, Therapy, Efficacy, Safety

The primary objective of this trial is to evaluate safety and tolerability of EO4010 in combination with nivolumab and/or with bevacizumab in patients with unresectable, previously treated locally advanced or mCRC.

Secondary objectives 1

1. The secondary objectives include assessment of immunogenicity in relation to T cells of each peptide composing EO4010; T cell cross-reactivity with the human tumor associated antigens (TAAs), objective response rate (ORR), disease control rate (DCR), time to response (TTR), and duration of response (DOR), progression-free survival (PFS) and PFS rate at 4 months, and overall survival (OS)

Conditions and MedDRA coding

Patients with unresectable, previously treated locally advanced or metastatic colorectal carcinoma.

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. HLA-A2 positive patients with advanced non-resectable colorectal adenocarcinoma which is mismatch repair proficient and microsatellite stable, who have been previously treated with, or are not considered candidates therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents
2. Progression during or within 3 months following the latest administration of standard therapies (outlined above)
3. at an age ≥ 18 years
4. ECOG performance status 0 to 1.

Exclusion criteria 9

1. patients treated with dexamethasone > 2 mg/day or equivalent (i.e., 13 mg/day of prednisone) within 14 days before first administration of EO4010
2. who have received any prior treatment with compounds targeting PD1, PD-L1, CTLA-4, or similar compounds, trifluridine/tipiracil (TAS-102) or regorafenib
3. treated with radiotherapy within 12 weeks, and cytotoxic chemotherapy therapy within 28 days (or 5 half-lives of the compound(s) administered if longer) before study treatment start
4. With persistent Grade ≥ 2 toxicities (according to NCI-CTCAE v5.0). except alopecia, neuropathy, and other persisting toxicities not constituting a safety risk based on Investigator’s judgment
5. With uncontrolled central nervous system (CNS) metastasis
6. with the significant abnormal laboratory values hematology, liver and renal function
7. with clinically significant active infection, cardiac disease, significant medical or psychiatric disease/condition that, in the opinion of the Investigator, would interfere with the interpretation of patient safety or study results or that would prohibit the understanding or rendering of informed consent
8. Patients with a history of solid organ transplantation or allogeneic hematopoietic stem cell transplantation
9. history or presence of human immunodeficiency virus (HIV) and/or active hepatitis B virus (HBV)/hepatitis C virus (HCV).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint includes safety and tolerability of EO4010 in combination with nivolumab, and/or with bevacizumab by a descriptive medical assessment of the combined profile of incidences of adverse events (AEs), treatment-emergent AEs (TEAEs), serious AEs (SAEs), deaths, reasons for treatment discontinuation/delays, and laboratory abnormalities using the NCI-CTCAE v5.0 grading system.

Secondary endpoints 8

1. percentage of patients with shown immunogenicity (expansion of specific T cells comparing samples taken at baseline versus on treatment in an individual patient determining if the patient has a positive response to the immunization, or not) in relation to each peptide composing EO4010 by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot), and by intracellular cytokines staining, or multimers staining assays.
2. Cross-reactivities with the human TAAs.
3. ORR
4. DCR
5. TTR
6. DOR and
7. PFS as described by RECIST 1.1 and iRECIST criteria.
8. OS

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Enterome

Sponsor organisation

Enterome

Address

94 Avenue Ledru Rollin

City

Paris

Postcode

75011

Country

France

Scientific contact point

Organisation

Enterome

Contact name

Enterome SA Medical

Public contact point

Organisation

Enterome

Contact name

Enterome SA Medical

Third parties 13

Locations

2 EU/EEA countries · 5 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 5 files

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

Application history

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