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
Overview
- Phase
- Phase 1
- Intervention
- Multiple dose of EO2401
- Conditions
- Glioblastoma, Adult
- Sponsor
- Enterome
- Enrollment
- 100
- Locations
- 10
- Primary Endpoint
- Safety and Tolerability of EO2401 Monotherapy, EO2401 in Combination With Nivolumab , EO2401 in Combination With Nivolumab and Bevacizumab
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
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 vaccination approaches might have developed; also, patients should not have received systemic anti-tumor treatment or radiotherapy for their progressive or first recurrent GB.
- •Patients with tumors primarily located in the infra-tentorial segment
- •Patients with known radiological evidence of extracranial metastases
- •Patients with presence of new hemorrhage (excluding, stable Grade 1) or uncontrolled seizure
- •Patients with significant leptomeningeal disease
- •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:
- •Hemoglobin \< 10 g/dL (6.2 mmol/L)
- •White blood cell count decrease (\< 3.0 × 109/L) or increase (\> 10.0 × 109/L)
- •Absolute neutrophil count decrease (\< 1.5 × 109/L)
Arms & Interventions
Cohort 1
Multiple dose of EO2041 monotherapy followed by continued EO2401 in combination with nivolumab
Intervention: Multiple dose of EO2401
Cohort 2
Multiple dose of EO2041 in combination with nivolumab
Intervention: Multiple dose of EO2401
Cohort 3
Multiple dose of EO2041 in combination with nivolumab and bevacizumab
Intervention: Multiple dose of EO2401
Outcomes
Primary Outcomes
Safety and Tolerability of EO2401 Monotherapy, EO2401 in Combination With Nivolumab , EO2401 in Combination With Nivolumab and Bevacizumab
Time Frame: From treatment start up to study end, assessed up to 44 months
Incidences of deaths
Secondary Outcomes
- Evaluation of Survival(From treatment start up to study end, assessed up to 44 months)
- Assessment of the Immunogenicity of EO2316, EO2317, EO2318 (Three Components of the Therapeutic Vaccine), and Universal Cancer Peptide That Compose EO2401(6 weeks after treatment start)