A clinical trial to investigate EO4010, a novel cancer vaccine therapy, with an immune checkpoint blocker, in patients with previously treated metastatic colorectal carcinoma.
- Conditions
- Patients with unresectable, previously treated locally advanced or metastatic colorectal carcinoma.MedDRA version: 21.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10010036Term: Colorectal carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-002805-90-ES
- Lead Sponsor
- Enterome SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 42
1. Provided written informed consent prior to any study-related procedures (initial consent is for screening part #1 procedures, and a second consent is for screening part #2 procedures; see Protocol Section 7.2 and Section 7.3, respectively). Patients must be able to understand and be willing to sign a written informed consent.
2. Histological confirmation of advanced non-resectable colorectal adenocarcinoma (confirmation at initial diagnosis is sufficient) which is mismatch repair proficient and microsatellite stable (according to local site standard testing procedures), i.e. patients with mismatch repair deficient or microsatellite instability-high metastatic disease cannot be recruited to this trial.
3. Patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for (according to the judgement of the recruiting site physician; e.g., due to progression or unacceptable toxicity on the type of treatment, or type of treatment not indicated in the specific patient due to his/her disease characteristics - when appropriate a collaborative discussion between the recruiting physician and the Medical Monitor should be held to keep the study population consistent), therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.
4. Progression during or within 3 months following the latest administration of standard therapies as outlined in inclusion criterion #3.
5. Age = 18 years old.
6. Human leukocyte antigen (HLA)-A2 positive.
7. ECOG performance status 0 or 1 (see Protocol Section 12.1).
8. Measurable disease according to Response Evaluation Criteria in Solid Tumors criteria (RECIST), version 1.1.
9. Patients with a life expectancy of at least 3 months as judged by the recruiting site physician.
10. Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to randomization.
11. Considering the embryofetal toxicity of the immune checkpoint inhibitor (ICI) shown in animals’ models, the following recommendations for contraception must be followed:
a. If not surgically sterile, female patients of childbearing potential age must use highly effective contraception from signing the Informed Consent Form (ICF) through 6 months after the last treatment dose administered. Highly effective contraception includes (according to Clinical Trial Facilitation Group: Recommendations related to contraception and pregnancy testing in clinical trials):
i. combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal,
ii. progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable,
iii. intrauterine device (IUD),
iv. intrauterine hormone-releasing system (IUS),
v. bilateral tubal occlusion,
vi. vasectomized partner, and
vii. sexual abstinence when in line with the preferred and usual lifestyle of the patient (e.g. periodic abstinence is not considered a highly effective method).
In each case of delayed menstrual period (over 1 month between menstruations), confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles.
b. If not surgically sterile, male with female partner of childbearing potential age must use condom from signing the ICF through 6
1. Patients treated with dexamethasone > 2 mg/day or equivalent (i.e., 13 mg/day of prednisone) within 14 days before randomization, unless required to treat an adverse event (AE).
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, CTLA-4, or similar compounds where general resistance against therapeutic vaccination approaches might have developed.
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, the current trial compound.
7. Patients with the following abnormal laboratory values:
a. Lymphocyte count decreased, grade 2 (lymphocytes <800 - 500/mm3; <0.8 - 0.5 x 10^9/L), or worse grade.
b. Hemoglobin < 10 g/dL (6.2 mmol/L); transfusion is acceptable to reach the value.
c. Absolute neutrophil count decrease (<1.5 x10^9/L).
d. Platelet count decrease (< 75 ×10^9/L).
e. Total bilirubin > 1.5 ×upper limit of normal (ULN; according to the performing laboratory’s reference ranges); except participants with Gilbert Syndrome who must have a total bilirubin level of < 3.0 xULN.
f. Alanine aminotransferase (ALT) > 3 ×ULN; if disease metastatic to the liver > 5 xULN.
g. Aspartate aminotransferase (AST) > 3 ×ULN; if disease metastatic to the liver > 5 xULN.
h. Serum creatinine increase (> 1.5 ×ULN).
i. 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 such as basal cell or squamous cell skin cancer, or carcinoma in situ.
9. 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 and compliance with the requirements of the protocol – including (but not limited to):
a. Bacterial sepsis, COVID-19, or other similarly severe infections (clinical assessment is the basis for exclusion of severe infections; if clinical suspicion, adequate testing should be performed to exclude severe infections).
b. New York Heart Association > Grade 2 congestive heart failure within 6 months prior to randomization (see Protocol Section 12.2).
c. Uncontrolled or significant cardiovascular disease
d. Stroke within 6 months prior to randomization.
e. Concurrent neurodegenerative disease.
f. Dementia or significantly altered mental status.
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. Patient
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method