First-in-Human, Phase 1b/2a Trial of a Multipeptide Therapeutic Vaccine in Patients With Progressive Glioblastoma

Inclusion Criteria

• Patients with unequivocal documented (including histological confirmation of Glioblastoma-GB- at the primary diagnosis) evidence of first progression/recurrence of GB on MRI, as defined by RANO criteria
• Patients with :
• for Cohorts 1, 2a, and 3: at least 1 measurable lesion
• for Cohort 2b: no measurable enhancing disease
• for Cohort 2c: documented recurrence of GB deemed to be candidate for surgery
• Patients with an age ≥ 18 years old
• Patients who are human leukocyte antigen (HLA)-A2 positive
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 or Karnofsky performance status ≥ 70
• Patients should have received standard primary therapy, including surgery (biopsy, incomplete or complete resection), radiation, temozolomide, if applicable
• Radiation therapy must have been finished 28 days before first study treatment administration
• 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)
• 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)
• Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to dosing
• 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 contraception from signing the Informed Consent Form (ICF) through 6 months after the last treatment dose administered. Highly effective 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 contraception also.

• Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures
• 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 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 implios the patient should not receive treatment with dexamethasone > 2 mg/day or equivalent at the actual time of a screening visit (single time point assessment), and within 14 days before the first EO2401 administration (unless required to treat AE); the latter part of the criterion should be checked at the time of treatment start.
• 2. Patients treated with radiotherapy, and cytoreductive therapy within 28 days (6 weeks for nitrosoureas) before the first EO2401 administration. In addition, patients should not have received any prior treatment with compounds targeting PD-1, PD-L1, CTLA-4, or similar compounds where general resistance against therapeutic vaccinat