The purpose of this study is to assess the safety, tolerability, immunogenicity, and
preliminary efficacy of EO2401 in patients with unequivocal evidence of progressive or first
recurrent glioblastoma.
This is a multicenter, Phase 1b/2a, First-In-Human study to assess the safety, tolerability,
immunogenicity, and preliminary efficacy of EO2401 in patients with unequivocal evidence of
progressive or first recurrent glioblastoma.
EO2401 is an innovative cancer peptide therapeutic vaccine based on the homologies between
Tumor Associated Antigens and microbiome-derived peptides that will be administered alone and
in combination with nivolumab, and nivolumab/bevacizumab to generate preliminary safety and
efficacy data in patients with progressive glioblastoma.
Inclusion Criteria:
1. Patients with unequivocal documented (including histological confirmation of
Glioblastoma-GB- at the primary diagnosis) evidence of progressive or first recurrent
GB on MRI, as defined by RANO criteria
2. Patients with at least 1 measurable lesion
3. Patients with an age ≥ 18 years old
4. Patients who are human leukocyte antigen (HLA)-A2 positive
5. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 or
Karnofsky performance status ≥ 70
6. Patients should have received standard therapy, including surgery (biopsy, incomplete
or complete resection), radiation, temozolomide, if applicable
1. Radiation therapy must have been finished 28 days before first study treatment
administration
2. Patients who received temozolomide as adjuvant therapy must have stopped the
treatment and have a wash-out period of 28 days before first study treatment
administration (6 weeks for nitrosoureas and 5 half lives for experimental
therapies)
3. Patients with unmethylated methylguanine-DNA-methyltransferase (MGMT) promoter
can be included even if they have not received temozolomide prior to the
inclusion in this clinical study)
7. Female patients of childbearing potential must have a negative serum pregnancy test
within 72 hours prior to dosing
8. Considering the embryofetal toxicity of the nivolumab shown on 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 barrier contraception from signing the Informed Consent Form (ICF)
through 6 months after the last treatment dose administered. Highly effective barrier
and non barrier contraception included: 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 iv.
Intrauterine hormone-releasing system v. Bilateral tubal occlusion vi. Sexual
abstinence. 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 must
use condom from signing the ICF through 8 months after the last treatment dose
administered. Males must ensure that their partners of childbearing potential use
highly effective barrier contraception also.
9. Patients having received the information sheet and who have provided written informed
consent prior to any study-related procedures
10. Patients willing and able to comply with the scheduled visits, treatment plan,
laboratory tests, and other study procedures indicated in the protocol.
Exclusion Criteria:
1. Patients treated with dexamethasone > 2 mg/day or equivalent (i.e., 13 mg/day of
prednisone) within 14 days before the first EO2401 administration, unless required to
treat an adverse event (AE) Note: The criterion is applicable at the time of screening
and also at the time of study treatment start (i.e. the patient should not have
received treatment with dexamethasone > 2 mg/day or equivalent in the time between
screening and study treatment start; this should be checked at the time of treatment
start).
2. Patients treated with PD (L)-1(Programmed-cell Death/Programmed-cell Death Ligand)
immunotherapy, radiotherapy, and cytoreductive therapy within 28 days before the first
EO2401 administration
3. Patients with tumors primarily located in the infra-tentorial segment
4. Patients with known radiological evidence of extracranial metastases
5. Patients with presence of new hemorrhage (excluding, stable Grade 1) or uncontrolled
seizure
6. Patients with significant leptomeningeal disease
7. Patients with abnormal (≥ Grade 2 National Cancer Institute-Common Terminology
Criteria for AEs [NCI-CTCAE] version 5.0) laboratory values for hematology, liver, and
renal function (serum creatinine). In detail, the following values apply as exclusion
criteria:
1. Hemoglobin < 10 g/dL (6.2 mmol/L)
2. White blood cell count decrease (< 3.0 × 109/L) or increase (> 10.0 × 109/L)
3. Absolute neutrophil count decrease (< 1.5 × 109/L)
4. Platelet count decrease (< 75 × 109/L)
5. Bilirubin > 1.5 × upper limit of normal (ULN; according to the performing
laboratory's reference ranges)
6. Alanine aminotransferase > 3 × ULN
7. Aspartate aminotransferase > 3 × ULN
8. Gamma-glutamyltransferase > 2.5 × ULN
9. Serum creatinine increase (> 1.5 × ULN)
10. Abnormal thyroid function: 0.3 > thyroid-stimulating hormone > 5 μU(μunit)/mL and
1.07 > free T3 > 3.37 nmol/L and 8.6 > free T4 > 25 pmol/L.
8. For patients who are planned to receive bevacizumab:
1. Patients with nephrotic syndrome
2. Patients with proteinuria ≥ 2g/24 hours
3. Patients with history or active gastrointestinal perforation and fistula
4. Significant surgical procedure in the 4 weeks preceding the start of treatment or
planned surgery
5. Unhealed wound
6. Patient with recent (4 weeks) history of hemoptysis of ½ teaspoon or more of red
blood
7. Thrombotic episode within 6 months
8. Uncontrolled diabetes mellitus or hypertension
9. Posterior reversible encephalopathy syndrome
9. Patients with persistent Grade 3 or 4 toxicities (according to NCI-CTCAE v5.0).
Toxicities must be resolved since at least 2 weeks to Grade 1 or less. However,
alopecia or other persisting toxicities Grade ≤ 2 not constituting a safety risk based
on Investigator's judgment is acceptable
10. Patients with contraindication to contrast-enhanced MRI
11. Other malignancy or prior malignancy with a disease-free interval of less than 3 years
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.
Patients with adequately treated basal cell or squamous cell skin cancer, or carcinoma
in situ are eligible
12. Patients with clinically significant cardiac disease, significant medical or
psychiatric disease/condition that, in the opinion of the Investigator, would
interfere with the evaluation of EO2401 or 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):
1. New York Heart Association > Grade 2 congestive heart failure within 6 months
prior to study entry
2. Uncontrolled or significant cardiovascular disease, including:
i. Myocardial infarction within 6 months prior to obtaining informed consent ii.
Uncontrolled angina within 6 months prior to obtaining informed consent iii. Diagnosed
or suspected congenital long QT syndrome iv. Any history of clinically significant
ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or
Torsades de pointes) v. Unstable angina within 6 months prior to obtaining informed
consent. c. Stroke within 6 months prior obtaining informed consent d. Concurrent
neurodegenerative disease e. Dementia or significantly altered mental status.
13. Patients with suspected autoimmune or active autoimmune disorder or known history of
an autoimmune neurologic condition (e.g., Guillain-Barré syndrome)
14. Patients with vitiligo, type I diabetes mellitus, hypothyroidism due to autoimmune
condition only requiring hormone replacement therapy, psoriasis not requiring systemic
therapy, or conditions not expected to recur in the absence of an external trigger are
permitted to enroll
15. Patients with history of solid organ transplantation or hematopoietic stem cell
transplantation
16. Patients with history or known presence of tuberculosis
17. Pregnant and breastfeeding patients
18. Patients with history or presence of human immunodeficiency virus and/or hepatitis B
virus/hepatitis C virus
19. 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
20. Patients with a history of hypersensitivity to any excipient present in the
pharmaceutical form of investigational medicinal product
21. Patients treated with herbal remedies with immunostimulating properties or known to
potentially interfere with major organ function
22. Patients with known drug and alcohol abuse
23. Patients with known or underlying medical or psychiatric condition that, in the
Investigator's opinion, would make the administration of study drug hazardous to the
patient or obscure the interpretation of toxicity determination or AEs
24. Patients who have received treatment with any other investigational agent, or
participation in another clinical trial within 28 days prior to enrollment and during
the treatment period
25. Patients deprived of their liberty or under protective custody or guardianship.