EO4010 in Previously Treated Metastatic Colorectal Carcinoma

Colorectal Cancer Metastatic Clinical Trial

— AUDREY  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05589597
• Other study ID #: EOCRC2-22
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2023
• Est. completion date: February 2026

Study information

• Verified date: October 2023
• Source: Enterome
• Contact: Jan Fagerberg
• Phone: +32 3 205 55 55
• Email: medicalmonitoring-crc[@]enterome.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-label multicenter study

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms

Intervention

Drug:
• EO4010
Sequential assignment

Locations

Country	Name	City	State
France	Hôpital Jean Minjoz	Besançon
France	ICM Val d'Aurelle	Montpellier
France	Saint Antoine hospital	Paris
Spain	Hospital Universitari Vall d'Hebron	Barcelona
United States	MD Anderson	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Enterome

Countries where clinical trial is conducted

United States,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of EO4010 in combination with nivolumab	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.	12months
Secondary	Percentage of patients with shown immunogenicity	Immunogenicity will be assessed by Interferon-? ELISpot	12 months
Secondary	Overall response rate	Defined as the percentage of patients who have a partial or complete response following Response Evaluation Criteria in Solid Tumors criteria	12 months
Secondary	Disease control rate	Defined as the percentage of patients who have achieved complete response, partial response or stable disease following Response Evaluation Criteria in Solid Tumors criteria	12 months
Secondary	Time to response	Defined as the time interval from first study treatment administration to partial or complete response following Response Evaluation Criteria in Solid Tumors criteria	12 months
Secondary	Duration of response	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	12 months
Secondary	Progression free survival	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	4months
Secondary	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	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	12 months