EO4010 in Previously Treated Metastatic Colorectal Carcinoma

Study Overview
=================
Brief Summary
-----------------
Open-label multicenter study

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

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

Conditions
-----------------
Colorectal Cancer Metastatic

Intervention / Treatment
-----------------
* Drug: EO4010


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provided written informed consent Histological confirmation of advanced non-resectable colorectal adenocarcinoma Patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for Progression during or within 3 months following the latest administration of standard therapies Age ≥ 18 years old Human leukocyte antigen (HLA)-A2 positive ECOG performance status 0 or 1 Measurable disease according to Response Evaluation Criteria in Solid Tumors criteria (RECIST) Patients with a life expectancy of at least 3 months Female patients of childbearing potential must have a negative serum pregnancy test Patients following recommendations for contraception Patients willing and able to comply with the study procedures Exclusion Criteria: Patients treated with dexamethasone > 2 mg/day or equivalent within 14 days before randomization, unless required to treat an adverse event Patients treated with radiotherapy within 12 weeks, and cytotoxic chemotherapy therapy within 28 days 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 Patients who have received any prior treatment with compounds targeting PD1, PDL1, CTLA-4, or similar compounds Patients who have previously received trifluridine/tipiracil (TAS-102) or regorafenib Patients with prior exposure to EO2401, EO2040, or EO4010, i.e. therapeutic vaccine compounds including all or some components of EO4010 Patients with the following abnormal laboratory values: Lymphocyte count decreased, grade 2 (lymphocytes <800 - 500/mm3; <0.8 - 0.5 x 109/L), or worse grade Hemoglobin < 10 g/dL (6.2 mmol/L); transfusion is acceptable to reach the value Absolute neutrophil count decrease (<1.5 x109/L) Platelet count decrease (< 75 ×109/L) Total bilirubin > 1.5 ×upper limit of normal Alanine aminotransferase (ALT) > 3 ×ULN; if disease metastatic to the liver > 5 xULN Aspartate aminotransferase (AST) > 3 ×ULN; if disease metastatic to the liver > 5 xULN Serum creatinine increase (> 1.5 ×ULN) Abnormal thyroid function per local laboratory levels 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 Patients with clinically significant active infection, cardiac disease, significant medical or psychiatric disease/condition Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g., Guillain-Barré syndrome) Patients with a history of solid organ transplantation or allogeneic hematopoietic stem cell transplantation Patients with a history or known presence of tuberculosis Pregnant and breastfeeding patients Patients with a history or presence of human immunodeficiency virus (HIV) and/or active hepatitis B virus (HBV)/hepatitis C virus (HCV) Uncontrolled central nervous system (CNS) metastasis 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 Patients with a history of hypersensitivity to any excipient, or active substance, present in the pharmaceutical forms of applicable study treatments Patients under treatment with immunostimulatory or immunosuppressive medications Patients who have received treatment with any other investigational agent, or participation in another clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Multi-cohort
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>E04010 Monotherapy | Drug: EO4010<br>* Sequential assignment<br>* Other names: Nivolumab;|
| Experimental: Cohort 2<br>E04010 in combination with nivolumab | Drug: EO4010<br>* Sequential assignment<br>* Other names: Nivolumab;|
| Experimental: Cohort 3<br>E04010 in combination with nivolumab | Drug: EO4010<br>* Sequential assignment<br>* Other names: Nivolumab;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with shown immunogenicity | Immunogenicity will be assessed by Interferon-γ ELISpot | 12 months | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |