A Phase 1/2 Trial of a Novel Therapeutic Vaccine (EO2401) in Combination With Immune Check Point Blockade, for Treatment of Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma
Overview
- Phase
- Phase 1
- Intervention
- EO2401
- Conditions
- Adrenocortical Carcinoma
- Sponsor
- Enterome
- Enrollment
- 70
- Locations
- 12
- Primary Endpoint
- Treatment-Emergent Serious Adverse Events Assessment
- Status
- Terminated
- Last Updated
- 3 months ago
Overview
Brief Summary
This is a multicenter, Phase 1/2, First-In-Human study to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2401 in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma.
Detailed Description
EO2401 is an innovative cancer peptide therapeutic vaccine based on the homologies between Tumor Associated Antigens and microbiome-derived peptides that will be administered in combination with nivolumab to generate preliminary safety and efficacy data in patients with Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Main Inclusion Criteria:
- •For inclusion in Cohort 1 patients should have adrenocortical carcinoma(ACC), or malignant pheochromocytoma/paraganglioma (MPP), as defined below for Cohorts 2A and 3A.
- •For inclusion in Cohorts 2A and 2B patients should have histologically confirmed (at primary diagnosis) unresectable locally advanced or metastatic adrenocortical carcinoma.
- •For inclusion in Cohorts 3A and 3B patients should have histologically confirmed (at primary diagnosis) unresectable malignant (defined as metastatic disease, i.e. presence of chromaffin tissue in non-chromaffin organs) pheochromocytoma/paraganglioma, and RECIST defined progression should have been documented during a maximum of an 18-months period.
- •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 ≤
- •Patients with a life expectancy \> 4 months as judged by their treating physician.
- •Patients with at least one measurable lesion according to RECIST 1.
- •Males or non-pregnant, non-lactating, females.
Exclusion Criteria
- •Patients treated with dexamethasone \> 2 mg/day or equivalent (i.e. 13 mg/day of prednisone, or 53 mg/day of hydrocortisone) within 14 days before the first EO2401 administration, unless required to treat an adverse event.
- •Patients with prior treatment with immune check-point inhibitors
- •Patients with prior exposure to EO
- •Patients treated with immunotherapy (meaning immunostimulatory or immunosuppressive therapy; beside excluded, or allowed, compounds per other inclusion/exclusion criteria specifications), radionuclide therapy, radiotherapy, cytoreductive therapy, or received treatment with any other investigational agent within 28 days before the first EO2401 administration.
- •Patients with an initial diagnosis of ACC less than 9 months from start of screening part
- •Patients with ACC and any individual lesion according to RECIST 1.1 having a maximum diameter of more than 125 mm; irrespective if the lesion is proposed as a target lesion, or not, according to RECIST 1.
- •Patients with ACC with more than three organs involved by disease, combined with unresectable primary tumor.
- •Patients with ACC and uncontrolled hormonal secretion (according to the judgement of the treating physician).
- •Patients with MPP and uncontrolled blood pressure (according to the judgement of the treating physician).
- •Patients with abnormal laboratory values.
Arms & Interventions
5-cohort study design
Cohort 1:3-by-3 design of EO2401 in combination with nivolumab at standard dose. Three to 12 evaluable patients with adrenal carcinoma or progressive malignant pheochromocytoma/paraganglioma will be included depending on the safety profile of the administered treatments. Cohorts 2A (previously treated patients) and 2B (previously untreated patients): evaluation of EO2401in combination with nivolumab in 33 patients with adrenal carcinoma. Cohorts 3A (previously treated patients) and 3B (previously untreated patients) : evaluation of EO2401 combination with nivolumab in 20 patients (globally for both Cohorts 3A and 3B) with progressive malignant pheochromocytoma/ paraganglioma.
Intervention: EO2401
5-cohort study design
Cohort 1:3-by-3 design of EO2401 in combination with nivolumab at standard dose. Three to 12 evaluable patients with adrenal carcinoma or progressive malignant pheochromocytoma/paraganglioma will be included depending on the safety profile of the administered treatments. Cohorts 2A (previously treated patients) and 2B (previously untreated patients): evaluation of EO2401in combination with nivolumab in 33 patients with adrenal carcinoma. Cohorts 3A (previously treated patients) and 3B (previously untreated patients) : evaluation of EO2401 combination with nivolumab in 20 patients (globally for both Cohorts 3A and 3B) with progressive malignant pheochromocytoma/ paraganglioma.
Intervention: Nivolumab
randomized extension of Cohort 2A (3 arms): C2A-I
Randomized extension of Cohort 2A (65 patients using a 4:1:1 ratio): 43 patients belonging to this extension of Cohort 2A will be treated by EO2401 and nivolumab in combination.
Intervention: EO2401
randomized extension of Cohort 2A (3 arms): C2A-I
Randomized extension of Cohort 2A (65 patients using a 4:1:1 ratio): 43 patients belonging to this extension of Cohort 2A will be treated by EO2401 and nivolumab in combination.
Intervention: Nivolumab
randomized extension of Cohort 2A (3 arms): C2A-II
11 patients belonging to this extension of Cohort 2A will be treated by EO2401 alone.
Intervention: EO2401
randomized extension of Cohort 2A (3 arms): C2A-III
11 patients belonging to this extension of Cohort 2A who will be treated by nivolumab alone.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Treatment-Emergent Serious Adverse Events Assessment
Time Frame: 46 months maximum (from baseline up to study end)
Incidences of treatment-emergent serious adverse events using the National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0.
Treatment-Emergent Non-Serious Adverse Events
Time Frame: 46 months maximum (from baseline up to study end)
Incidences of treatment-emergent non-serious adverse events using the National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0.
All Cause Mortalities Assessment
Time Frame: 46 months maximum (from baseline up to study end)
Incidence of death
Secondary Outcomes
- Evaluation of Progression Free Survival(6 months after treatment start)
- Evaluation of Survival(46 months maximum (from baseline up to study end))
- Percentage of Patients With Immunogenicity Against EO2401(7 weeks after treatment start)