Clinical Trials /

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

NCT04116658

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: First-in-Human, Phase 1b/2a Trial of a Multipeptide Therapeutic Vaccine in Patients With Progressive Glioblastoma
  • Official Title: A Multicenter, Open-Label, First-in-Human, Phase 1b/2a Trial of EO2401, a Novel Multipeptide Therapeutic Vaccine, With and Without Check Point Inhibitor, Following Standard Treatment in Patients With Progressive Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: EOGBM1-18
  • NCT ID: NCT04116658

Conditions

  • Glioblastoma, Adult

Interventions

DrugSynonymsArms
Multiple dose of EO2401Cohort 1

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalMultiple dose of EO2041 monotherapy followed by continued EO2401 in combination with nivolumab
  • Multiple dose of EO2401
Cohort 2ExperimentalMultiple dose of EO2041 in combination with nivolumab
  • Multiple dose of EO2401
Cohort 3ExperimentalMultiple dose of EO2041 in combination with nivolumab and bevacizumab (US only)
  • Multiple dose of EO2401

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of EO2401: National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0
Time Frame:Up to 24 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Evaluation of survival
Time Frame:From end of treatment to at least 24 months after last patient enrollment
Safety Issue:
Description:Overall survival, defined as the time interval from the date of first study treatment administration to the date of death due to any cause
Measure:Assessment of the immunogenicity of EO2316, EO2317, EO2318 (Three components of the therapeutic vaccine), and Universal Cancer Peptide that compose EO2401
Time Frame:Up to 24 months
Safety Issue:
Description:Immunogenicity will be assessed by Interferon-γ ELISpot

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Enterome

Trial Keywords

  • Glioblastoma
  • Vaccine
  • Nivolumab
  • Bevacizumab
  • Safety
  • Tolerability

Last Updated

October 3, 2019