Adrenocortical Carcinoma, Paraganglioma, Pheochromocytoma
Conditions
Keywords
adrenocortical carcinoma, 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.
Interventions
BIOLOGICALEO2401
Multiple dose of EO2401
BIOLOGICALNivolumab
Multiple dose of nivolumab
Sponsors
Enterome
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Serious Adverse Events Assessment | 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 | 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 | 46 months maximum (from baseline up to study end) | Incidence of death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Progression Free Survival | 6 months after treatment start | Progression Free Survival according to iRECIST criteria at 6 months |
| Evaluation of Survival | 46 months maximum (from baseline up to study end) | Overall survival, defined as the time interval from the date of first study treatment administration to the date of death due to any cause |
| Percentage of Patients With Immunogenicity Against EO2401 | 7 weeks after treatment start | 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). |
Countries
Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, United States
Contacts
STUDY_DIRECTORJean-Michel Paillarse
Enterome
Participant flow
Recruitment details
Cohort 1 safety lead-in assessed safety and tolerability of EO2401 in combination with nivolumab during 4 weeks. Evaluable patients in Cohort 1 will be assessed as part of the planned Cohorts 2A (non-randomized) and 3A, respectively. The schedule of EO2401 and nivolumab administrations are the same in Cohorts 2A (non randomized) and Cohort 3A as in Cohort 1.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 54 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment Denmark | 0 participants |
| Region of Enrollment France | 7 participants |
| Region of Enrollment Germany | 2 participants |
| Region of Enrollment Italy | 5 participants |
| Region of Enrollment Netherlands | 13 participants |
| Region of Enrollment Spain | 0 participants |
| Region of Enrollment Sweden | 1 participants |
| Region of Enrollment United States | 0 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 21 / 26 | 5 / 13 | 1 / 2 | 2 / 4 | 6 / 7 | 9 / 13 | 0 / 5 |
| other Total, other adverse events | 26 / 26 | 13 / 13 | 2 / 2 | 4 / 4 | 7 / 7 | 13 / 13 | 5 / 5 |
| serious Total, serious adverse events | 5 / 26 | 4 / 13 | 1 / 2 | 0 / 4 | 1 / 7 | 4 / 13 | 2 / 5 |
Outcome results
None listed