A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma

NCT ID: NCT04187404

Last Updated: 2026-01-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-23

Study Completion Date

2024-10-02

Brief Summary

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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

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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.

Conditions

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Adrenocortical Carcinoma Pheochromocytoma Paraganglioma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

EO2401

Intervention Type BIOLOGICAL

Multiple dose of EO2401

Nivolumab

Intervention Type BIOLOGICAL

Multiple dose of 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.

Group Type EXPERIMENTAL

EO2401

Intervention Type BIOLOGICAL

Multiple dose of EO2401

Nivolumab

Intervention Type BIOLOGICAL

Multiple dose of 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.

Group Type EXPERIMENTAL

EO2401

Intervention Type BIOLOGICAL

Multiple dose of 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.

Group Type ACTIVE_COMPARATOR

Nivolumab

Intervention Type BIOLOGICAL

Multiple dose of nivolumab

Interventions

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EO2401

Multiple dose of EO2401

Intervention Type BIOLOGICAL

Nivolumab

Multiple dose of nivolumab

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. For inclusion in Cohort 1 patients should have adrenocortical carcinoma(ACC), or malignant pheochromocytoma/paraganglioma (MPP), as defined below for Cohorts 2A and 3A.
2. For inclusion in Cohorts 2A and 2B patients should have histologically confirmed (at primary diagnosis) unresectable locally advanced or metastatic adrenocortical carcinoma.
3. 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.
4. Patients with an age ≥ 18 years old.
5. Patients who are human leukocyte antigen (HLA)-A2 positive.
6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
7. Patients with a life expectancy \> 4 months as judged by their treating physician.
8. Patients with at least one measurable lesion according to RECIST 1.1.
9. Males or non-pregnant, non-lactating, females.
10. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
11. Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures.

Exclusion Criteria

1. 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.
2. Patients with prior treatment with immune check-point inhibitors
3. Patients with prior exposure to EO2401.
5. Patients with an initial diagnosis of ACC less than 9 months from start of screening part 2.
6. 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 1.1.
7. Patients with ACC with more than three organs involved by disease, combined with unresectable primary tumor.
8. Patients with ACC and uncontrolled hormonal secretion (according to the judgement of the treating physician).
9. Patients with MPP and uncontrolled blood pressure (according to the judgement of the treating physician).
10. Patients with abnormal laboratory values.
11. Patients with persistent Grade 3 or 4 toxicities.
12. Uncontrolled central nervous system (CNS) metastasis.
13. Other malignancy or prior malignancy with a disease-free interval of less than 3 years
14. Patients with clinically significant disease.
15. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barré syndrome).
16. Patients with history of solid organ transplantation or hematopoietic stem cell transplantation.
17. Patients with history or known presence of tuberculosis.
18. Pregnant and breastfeeding patients.
19. Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection.
20. 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.
21. Patients with a history of hypersensitivity to any excipient present in the pharmaceutical forms of the study treatments.
22. Patients treated with herbal remedies with immunostimulating properties or known to potentially interfere with major organ function.
23. Patients with known ongoing drug and alcohol abuse.
24. 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.
25. Patients deprived of their liberty, under protective custody, or guardship.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Enterome

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Michel Paillarse

Role: STUDY_DIRECTOR

Enterome

Locations

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MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Chu Lille

Lille, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Assistance Publique - Hôpitaux de Marseille - Hôpital Nord

Marseille, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Lmu Klinikum

München, , Germany

Site Status

Universitätsklinikum Würzburg

Würzburg, , Germany

Site Status

Azienda Ospedaliera Spedali Civili

Brescia, , Italy

Site Status

Amsterdam UMC, location VUmc

Amsterdam, , Netherlands

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Karolinska University Hospital

Stockholm, , Sweden

Site Status

Countries

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United States Denmark France Germany Italy Netherlands Spain Sweden

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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EOADR1-19

Identifier Type: -

Identifier Source: org_study_id

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