EO4010 in Previously Treated Metastatic Colorectal Carcinoma (AUDREY)

• ClinicalTrials.gov Identifier: NCT05589597
• Recruitment Status: Recruiting
• First Posted: October 21, 2022
• Last Update Posted: October 23, 2023
• Sponsor: Enterome
• Information provided by (Responsible Party): Enterome

Study Description

Brief Summary:

Open-label multicenter study

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer Metastatic	Drug: EO4010	Phase 1; Phase 2

Detailed Description:

This is an open-label, multicenter, FIH, phase 1/2 trial to assess safety, tolerability, immunogenicity, and preliminary efficacy of the microbial-derived therapeutic vaccine EO4010 in combination with nivolumab for treatment of patients with unresectable, previously treated, metastatic colorectal cancer

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Multi-cohort
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Global Multicenter Phase 1/2 Trial of EO4010, a Novel Microbial Derived Peptide Therapeutic Vaccine, in Combination With Nivolumab, for Treatment of Patients With Previously Treated Metastatic Colorectal Carcinoma
• Actual Study Start Date: June 1, 2023
• Estimated Primary Completion Date: February 2026
• Estimated Study Completion Date: February 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; E04010 Monotherapy	Drug: EO4010; Sequential assignment; Other Name: Nivolumab
Experimental: Cohort 2; E04010 in combination with nivolumab	Drug: EO4010; Sequential assignment; Other Name: Nivolumab
Experimental: Cohort 3; E04010 in combination with nivolumab	Drug: EO4010; Sequential assignment; Other Name: Nivolumab

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of EO4010 in combination with nivolumab [ Time Frame: 12months ]
   Incidences of AEs, treatment-emergent AEs (TEAEs), Serious Adverse Events (SAEs), deaths, and laboratory abnormalities using the National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0.

Secondary Outcome Measures :

1. Percentage of patients with shown immunogenicity [ Time Frame: 12 months ]
   Immunogenicity will be assessed by Interferon-γ ELISpot
2. Overall response rate [ Time Frame: 12 months ]
   Defined as the percentage of patients who have a partial or complete response following Response Evaluation Criteria in Solid Tumors criteria
3. Disease control rate [ Time Frame: 12 months ]
   Defined as the percentage of patients who have achieved complete response, partial response or stable disease following Response Evaluation Criteria in Solid Tumors criteria
4. Time to response [ Time Frame: 12 months ]
   Defined as the time interval from first study treatment administration to partial or complete response following Response Evaluation Criteria in Solid Tumors criteria
5. Duration of response [ Time Frame: 12 months ]
   Defined as the time interval from first study treatment administration to disease progression or death in patients who achieve complete or partial response following Response Evaluation Criteria in Solid Tumors criteria
6. Progression free survival [ Time Frame: 4months ]
   Defined as the time interval from the date of first study treatment administration to the date of progression following Response Evaluation Criteria in Solid Tumors criteria
7. Overall survival to the date of death due to any cause. Patients alive will be censored at the date of the last documented follow-up [ Time Frame: 12 months ]
   Defined as the time interval from the date of first study treatment administration to the date of death due to any cause. Patients alive will be censored at the date of the last documented follow-up

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Provided written informed consent
2. Histological confirmation of advanced non-resectable colorectal adenocarcinoma
3. Patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for
4. Progression during or within 3 months following the latest administration of standard therapies
5. Age ≥ 18 years old
6. Human leukocyte antigen (HLA)-A2 positive
7. ECOG performance status 0 or 1
8. Measurable disease according to Response Evaluation Criteria in Solid Tumors criteria (RECIST)
9. Patients with a life expectancy of at least 3 months
10. Female patients of childbearing potential must have a negative serum pregnancy test
11. Patients following recommendations for contraception
12. Patients willing and able to comply with the study procedures

Exclusion Criteria:

1. Patients treated with dexamethasone > 2 mg/day or equivalent within 14 days before randomization, unless required to treat an adverse event
2. Patients treated with radiotherapy within 12 weeks, and cytotoxic chemotherapy therapy within 28 days
3. Patients with persistent Grade ≥ 2 toxicities (according to NCI-CTCAE v5.0). Toxicities must be resolved for at least 2 weeks to Grade 1 or less
4. Patients who have received any prior treatment with compounds targeting PD1, PDL1, CTLA-4, or similar compounds
5. Patients who have previously received trifluridine/tipiracil (TAS-102) or regorafenib
6. Patients with prior exposure to EO2401, EO2040, or EO4010, i.e. therapeutic vaccine compounds including all or some components of EO4010

7. Patients with the following abnormal laboratory values:

   1. Lymphocyte count decreased, grade 2 (lymphocytes <800 - 500/mm3; <0.8 - 0.5 x 109/L), or worse grade
   2. Hemoglobin < 10 g/dL (6.2 mmol/L); transfusion is acceptable to reach the value
   3. Absolute neutrophil count decrease (<1.5 x109/L)
   4. Platelet count decrease (< 75 ×109/L)
   5. Total bilirubin > 1.5 ×upper limit of normal
   6. Alanine aminotransferase (ALT) > 3 ×ULN; if disease metastatic to the liver > 5 xULN
   7. Aspartate aminotransferase (AST) > 3 ×ULN; if disease metastatic to the liver > 5 xULN
   8. Serum creatinine increase (> 1.5 ×ULN)
   9. Abnormal thyroid function per local laboratory levels
8. Other malignancy or prior malignancy with a disease-free interval of less than 3 years prior to ICF signing; except those treated with surgical intervention and an expected low likelihood of recurrence
9. Patients with clinically significant active infection, cardiac disease, significant medical or psychiatric disease/condition
10. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g., Guillain-Barré syndrome)
11. Patients with a history of solid organ transplantation or allogeneic hematopoietic stem cell transplantation
12. Patients with a history or known presence of tuberculosis
13. Pregnant and breastfeeding patients
14. Patients with a history or presence of human immunodeficiency virus (HIV) and/or active hepatitis B virus (HBV)/hepatitis C virus (HCV)
15. Uncontrolled central nervous system (CNS) metastasis
16. Patients who have received live or attenuated vaccine therapy used for prevention of infectious diseases including seasonal (influenza) vaccinations within 4 weeks of the first dose of study drug
17. Patients with a history of hypersensitivity to any excipient, or active substance, present in the pharmaceutical forms of applicable study treatments
18. Patients under treatment with immunostimulatory or immunosuppressive medications
19. Patients who have received treatment with any other investigational agent, or participation in another clinical trial

Contacts and Locations

Contacts

Contact: Jan Fagerberg; +32 3 205 55 55; medicalmonitoring-crc@enterome.com

Locations

United States, Texas

MD Anderson; Recruiting

Houston, Texas, United States, 77030

Contact: Arvind Dasari, MD 713-792-2828 adasari@mdandreson.org

France

Hôpital Jean Minjoz; Recruiting

Besançon, France, 25030

Contact: Christophe Borg, Pr +33 3 81 47 99 99 xtophe.borg@gmail.com

ICM Val d'Aurelle; Recruiting

Montpellier, France, 34298

Contact: Thibault Mazard, MD +33 4 67 61 31 36 Thibault.Mazard@icm.unicancer.fr

Saint Antoine hospital; Recruiting

Paris, France, 75012

Contact: Romain Cohen, MD romain.cohen@aphp.fr

Spain

Hospital Universitari Vall d'Hebron; Not yet recruiting

Barcelona, Spain, 08035

Contact: María Elena Élez Fernández, MD Phone : +34 93 274 60 85 Fax: meelez@vhio.net

Sponsors and Collaborators

Enterome

Investigators

• Study Director: Jan Fagerberg; Enterome

More Information

• Responsible Party: Enterome
• ClinicalTrials.gov Identifier: NCT05589597
• Other Study ID Numbers: EOCRC2-22
• First Posted: October 21, 2022
• Last Update Posted: October 23, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Colorectal Neoplasms; Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action