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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pheochromocytoma; Paraganglioma; Adrenocortical Carcinoma
• Intervention / Treatment: Biological: EO2401; Biological: Nivolumab

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
• France
  • Lille, France, 59037
    • Chu Lille
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13915
    • Assistance Publique - Hopitaux de Marseille - Hopital Nord
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Germany
  • München, Germany
    • LMU Klinikum
  • Würzburg, Germany, 97080
    • Universitatsklinikum Wurzburg
• Italy
  • Brescia, Italy, 25121
    • Azienda Ospedaliera Spedali Civili
• Netherlands
  • Amsterdam, Netherlands, 1081
    • Amsterdam UMC, location VUmc
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main 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.

Main 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.
4. 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.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: EO2401; Multiple dose of EO2401; Biological: Nivolumab; Multiple dose of nivolumab
Experimental: 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.	Biological: EO2401; Multiple dose of EO2401; Biological: Nivolumab; Multiple dose of nivolumab
Experimental: randomized extension of Cohort 2A (3 arms): C2A-II; 11 patients belonging to this extension of Cohort 2A will be treated by EO2401 alone.	Biological: EO2401; Multiple dose of EO2401
Active Comparator: 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.	Biological: Nivolumab; Multiple dose of nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Serious Adverse Events Assessment	Incidences of treatment-emergent serious adverse events using the National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0.	46 months maximum (from baseline up to study end)
Treatment-Emergent Non-Serious Adverse Events	Incidences of treatment-emergent non-serious adverse events using the National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0.	46 months maximum (from baseline up to study end)
All Cause Mortalities Assessment	Incidence of death	46 months maximum (from baseline up to study end)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Progression Free Survival	Progression Free Survival according to iRECIST criteria at 6 months	6 months after treatment start
Evaluation of Survival	Overall survival, defined as the time interval from the date of first study treatment administration to the date of death due to any cause	46 months maximum (from baseline up to study end)
Percentage of Patients With Immunogenicity Against EO2401	Expansion of specific T cells comparing samples taken at baseline versus on treatment in an individual patient determining if the patient has a positive response to peptides that compose EO2401, or not. EO2401 immunogenicity is assessed by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) (IVS and ex vivo).	7 weeks after treatment start

Collaborators and Investigators

• Sponsor: Enterome
• Investigators: Study Director: Jean-Michel Paillarse, Enterome

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Actual): October 2, 2024
• Study Completion (Actual): October 2, 2024

Study Registration Dates

• First Submitted: December 3, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: pheochromocytoma; adrenocortical carcinoma; paraganglioma
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Pheochromocytoma; Adrenocortical Carcinoma; Paraganglioma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: EOADR1-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Safety and efficacy data
• IPD Sharing Time Frame: Oct 2025
• IPD Sharing Access Criteria: Primary and key secondary outcomes
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No