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

• ClinicalTrials.gov Identifier: NCT04187404
• Recruitment Status: Recruiting
• First Posted: December 5, 2019
• Last Update Posted: February 21, 2023
• Sponsor: Enterome
• Information provided by (Responsible Party): Enterome

Tracking Information

• First Submitted Date: December 3, 2019
• First Posted Date: December 5, 2019
• Last Update Posted Date: February 21, 2023
• Actual Study Start Date: July 23, 2020
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 5, 2019)

Adverse events assessment [ Time Frame: Up to 24 months ]

Incidences of adverse events(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.

Original Primary Outcome Measures (submitted: December 4, 2019)

Safety and tolerability [ Time Frame: Up to 24 months ]

Incidences of adverse events(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.

Current Secondary Outcome Measures (submitted: January 27, 2023)

• Evaluation of Progression Free Survival at 6 months [ Time Frame: 6 months after first treatment date from the last patient enrolled ]
  Progression Free Survival according to iRECIST criteria defined as the time interval from the date of first study treatment administration to 6 months after
• Evaluation of survival [ Time Frame: From end of treatment to at least 24 months after last patient enrollment ]
  Overall survival, defined as the time interval from the date of first study treatment administration to the date of death due to any cause
• Assessment of the immunogenicity [ Time Frame: Up to 24 months ]
  Assessment of the immunogenicity of the 4 components that compose EO2401 Immunogenicity will be assessed by Interferon-γ ELISpot

Original Secondary Outcome Measures (submitted: December 4, 2019)

• Evaluation of survival [ Time Frame: From end of treatment to at least 24 months after last patient enrollment ]
  Overall survival, defined as the time interval from the date of first study treatment administration to the date of death due to any cause
• Assessment of the immunogenicity [ Time Frame: Up to 24 months ]
  Assessment of the immunogenicity of the 4 components that compose EO2401 Immunogenicity will be assessed by Interferon-γ ELISpot

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma
• Official Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Adrenocortical Carcinoma
• Pheochromocytoma
• Paraganglioma

Intervention

• Biological: EO2401
  Multiple dose of EO2401
• Biological: Nivolumab
  Multiple dose of nivolumab

Study Arms

• 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.

  Interventions:

  • Biological: EO2401
  • Biological: 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.
  Interventions:

  • Biological: EO2401
  • Biological: 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.
  Intervention: Biological: 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.
  Intervention: Biological: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 27, 2023): 120
• Original Estimated Enrollment (submitted: December 4, 2019): 72
• Estimated Study Completion Date: December 30, 2024
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jean-Michel Paillarse; +32 3 205 55 55; medicalmonitoring@enterome.com

• Listed Location Countries: Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, United States

Administrative Information

• NCT Number: NCT04187404
• Other Study ID Numbers: EOADR1-19
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Enterome
• Original Responsible Party: Same as current
• Current Study Sponsor: Enterome
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Jean-Michel Paillarse; Enterome

• PRS Account: Enterome
• Verification Date: February 2023