Colorectal Cancer
Conditions
Brief summary
The current study will evaluate the microbiome-derived therapeutic vaccine EO2040 in combination with nivolumab in patients with circulating tumor DNA-defined Minimal Residual Disease (MRD) of colorectal cancer stage II, III, or IV after completion of standard curative therapy.
Detailed description
The microbiome-derived therapeutic vaccine concept utilized in conjunction with anti-Programmed cell Death protein 1 (PD1) blockade is an innovative option for testing of a rational immunotherapy in colorectal cancer. The concept as such, including the combination with nivolumab, has already been tested in the clinical setting (i.e. in recurrent glioblastoma and adrenal tumors) and shown to be well tolerated.
Interventions
DRUGEO2040
EO2040, is a therapeutic peptide vaccine composed of two microbial-derived peptides mimicking cytotoxic T cell (CD8+ T cell) epitopes from the Tumor Associated Antigens (TAAs) combined with the helper peptide (CD4+ T cell epitope) Universal Cancer Peptide 2 (UCP2). The peptide mix EO2040, i.e. drug product (DP), will be emulsified with the adjuvant Montanide. EO2040 will be given in combination with nivolumab, which is an anti-PD1. Nivolumab is approved for use for the treatment of multiple cancer types, including subtypes of CRC (mismatch repair deficient or microsatellite instability-high metastatic disease after prior treatment). However, it is not currently approved for ctDNA defined MRD of CRC.
Sponsors
Enterome
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible to receive study treatment, a patient must meet all the criteria below: 1. Provided written informed consent prior to any study-related procedures . 2. Histological confirmation of colorectal cancer. 3. Post R0-resection of stages II, III, or IV CRC and completion of all planned standard of care adjuvant therapies. 4. Presence of minimal residual disease as defined by a positive ctDNA assay after completion of all planned standard of care therapies. 5. Age ≥ 18 years old. 6. Human leukocyte antigen (HLA)-A2 positive. 7. No evidence of radiographic disease 8. Predefined performance status 9. Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to randomization. 10. Considering the embryofetal toxicity of the immune checkpoint inhibitor (ICI) shown in animals' models, recommendations for contraception must be followed. 11. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
Exclusion criteria
Patients who meet any of the following criteria will not be eligible to participate in the study: 1. Patients treated with dexamethasone \> 2 mg/day or equivalent . 2. Patients 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. 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. However, alopecia, neuropathy, and other persisting toxicities not constituting a safety risk based on Investigator's judgment are acceptable. 4. Patients who have received any prior treatment with compounds targeting PD1, PD-L1, Cytotoxic T-lymphocyte-associated Antigen 4 (CTLA-4), or similar compounds where general resistance against therapeutic vaccination approaches might have developed. 5. Patients with defined abnormal laboratory values: 6. Patients with presence of other concomitant active, invasive malignancies . 7. Patients 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 suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g., Guillain-Barré syndrome).. 9. Patients with a history of solid organ transplantation or allogeneic hematopoietic stem cell transplantation. 10. Patients with a history or known presence of tuberculosis. 11. Pregnant and breastfeeding patients. 12. Patients with a history or presence of human immunodeficiency virus (HIV) and/or active hepatitis B virus (HBV)/hepatitis C virus (HCV). 13. 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. 14. Patients with a history of hypersensitivity to any excipient, or active substance, present in the pharmaceutical forms of applicable study treatments. 15. Patients under treatment with immunostimulatory or immunosuppressive medications, including herbal remedies, or herbal remedies known to potentially interfere with major organ function. 16. Patients who have received treatment with any other investigational agent, or participation in another clinical trial \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response to Treatment at 6 Months | 6 months | Percentage of patients with ctDNA clearance and no radiographic evidence of recurrence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events | 7 months | Number and percentage of patients with Serious Adverse Events (SAEs ) |
| NCI-CTCAE Grading | 7 months | Number and percentage of patients with at least one NCI-CTCAE v5.0 grade increase or decrease |
| Response to Therapy at 3 Months | 3 months | Percentage of patients with ctDNA clearance and no radiographic evidence of recurrence |
| Treatment-Emergent Adverse Events | 7 months | Number and percentage of patients with Treatment-Emergent Adverse Events (TEAEs) |
| Overall Survival | 7 months | Overall survival (OS), measured as the time from start of study treatment until death from any cause. |
| Immunogenicity and Cross-reactivity | 6 months | Percentage of patients with a positive tetramer staining in peripheral blood mononuclear cells for the two microbial-derived peptides which are part of the therapeutic vaccine EO2040. |
| DIsease-free Survival | 7 months | Disease-free survival (DFS) defined as the time from start of study treatment to the date of first documented colorectal cancer (CRC) recurrence or death due to any cause, |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With Minimal Residual Disease of Colorectal Cancer Patients With Circulating Tumor DNA-defined Minimal Residual Disease of Colorectal Cancer Stage II, III, or IV After Completion of Curative Therapy
EO2040: EO2040, is a therapeutic peptide vaccine composed of two microbial-derived peptides mimicking cytotoxic T cell (CD8+ T cell) epitopes from the Tumor Associated Antigens (TAAs) combined with the helper peptide (CD4+ T cell epitope) Universal Cancer Peptide 2 (UCP2).
The peptide mix EO2040, i.e. drug product (DP), will be emulsified with the adjuvant Montanide.
EO2040 will be given in combination with nivolumab, which is an anti-PD1. Nivolumab is approved for use for the treatment of multiple cancer types, including subtypes of CRC (mismatch repair deficient or microsatellite instability-high metastatic disease after prior treatment). However, it is not currently approved for ctDNA defined MRD of CRC. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Patients With Minimal Residual Disease of Colorectal Cancer |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 0 |
| BMI | 39 kg/m2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Response to Treatment at 6 Months
Percentage of patients with ctDNA clearance and no radiographic evidence of recurrence
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Minimal Residual Disease of Colorectal Cancer | Response to Treatment at 6 Months | 0 Participants |
Secondary
DIsease-free Survival
Disease-free survival (DFS) defined as the time from start of study treatment to the date of first documented colorectal cancer (CRC) recurrence or death due to any cause,
Time frame: 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Minimal Residual Disease of Colorectal Cancer | DIsease-free Survival | 14 weeks |
Secondary
Immunogenicity and Cross-reactivity
Percentage of patients with a positive tetramer staining in peripheral blood mononuclear cells for the two microbial-derived peptides which are part of the therapeutic vaccine EO2040.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Minimal Residual Disease of Colorectal Cancer | Immunogenicity and Cross-reactivity | 1 Participants |
Secondary
NCI-CTCAE Grading
Number and percentage of patients with at least one NCI-CTCAE v5.0 grade increase or decrease
Time frame: 7 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Minimal Residual Disease of Colorectal Cancer | NCI-CTCAE Grading | 1 Participants |
Secondary
Overall Survival
Overall survival (OS), measured as the time from start of study treatment until death from any cause.
Time frame: 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Minimal Residual Disease of Colorectal Cancer | Overall Survival | 7 months |
Secondary
Response to Therapy at 3 Months
Percentage of patients with ctDNA clearance and no radiographic evidence of recurrence
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Minimal Residual Disease of Colorectal Cancer | Response to Therapy at 3 Months | 0 Participants |
Secondary
Serious Adverse Events
Number and percentage of patients with Serious Adverse Events (SAEs )
Time frame: 7 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Minimal Residual Disease of Colorectal Cancer | Serious Adverse Events | 1 Participants |
Secondary
Treatment-Emergent Adverse Events
Number and percentage of patients with Treatment-Emergent Adverse Events (TEAEs)
Time frame: 7 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Minimal Residual Disease of Colorectal Cancer | Treatment-Emergent Adverse Events | 1 Participants |