None listed
Conditions
Interventions
Product Code: EO2401
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: EO2316 - SUB205540
CAS Number: N/A
Current Sponsor code: EO2316
Other descriptive name: EO2316
Concentration unit:
Sponsors
Enterome
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. For inclusion in Cohort 1 patients should have adrenocortical carcinoma, or malignant pheochromocytoma/paraganglioma, 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 (ENSAT/AJCC] stage 3 = tumor has spread into nearby tissues or lymph nodes, or stage 4 = metastatic disease) adrenocortical carcinoma. a. In addition, for inclusion in Cohort 2 A patients should also have received treatment with at least one line, but not more than two prior lines, of systemic therapy for established locally advanced or metastatic disease (i.e. non-adjuvant therapy). b. In addition, for inclusion in Cohort 2B patients should not have received prior systemic therapy for established locally advanced or metastatic disease (i.e. non-adjuvant therapy). Note, for both Cohorts 2A and 2B, adjuvant therapy (including mitotane with or without chemotherapy) for patients after complete response to local therapy (e.g. resection) should not be counted in the definitions above for line of therapy for established disease. Patients who have received mitotane as adjuvant therapy can continue mitotane during study therapy provided tumor recurrence has been demonstrated at mitotane therapeutic plasma level (> 14 mg/L) or at maximum individual tolerated dose. 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 18months period. a. In addition, for inclusion in Cohort 3A patients should also have received treatment with at least two prior lines of systemic therapy if the patients are eligible for radionuclide therapy, and at least one prior line of systemic therapy if the patients are not eligible for radionuclide therapy. b. In addition, for inclusion in Cohort 3B patients should not have received prior systemic therapy for their malignant pheochromocytoma/paraganglioma. 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 = 2 (see Section 12.2 [39]). 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 (see Section 12.1). 9. Males or non-pregnant, non-lactating, females who are: a) female, post-menopausal (serum follicle-stimulating hormone (FSH) level > 40 mIU/mL ), b) female and male, surgically sterile (e.g. bilaterally blocked or removed fallopian tubes, vas deferens), c) female of childbearing potential with a negative highly sensitive serum pregnancy test within 72 hours prior to first administration of study treatment and use of a highly effective contraception from signing the Informed Consent Form (ICF) through 5 months after the last study treatment dose administered; note, the male partner should in addition to the use of highly effective contraception by the female patient also use condoms, d) male patient with female partners of childbearing potential must use condoms from signing the ICF through 5 months after the last study treatment dose administered; in addition, male p
Exclusion criteria
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. Note, inhaled steroids and adrenal replacement steroid doses > 13 mg daily prednisone equivalents are permitted. Thus, patients needing hydrocortisone replacement therapy due to prior or ongoing mitotane therapy can receive hydrocortisone doses > 53 mg/day, i.e. also in the normally used range of 60-80 mg/day, and still be included in the trial. 2. Patients with prior treatment with compounds targeting PD-1, PD-L1, CTLA-4, or similar compounds where general resistance against therapeutic vaccination approaches might have developed (e.g. defects to the cellular antigen processing/presentation machinery, including mutations in Janus kinas [JAK] 1, JAK2, and ß-2-microglobulin [B2M]) allowing tumor cells to avoid recognition and attack by immune cells. 3. Patients with prior exposure to EO2401, e.g. patients treated in Cohorts 2B or 3B of the current trial cannot be re-enrolled for treatment also in Cohorts 2A or 3A. 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. Note, for patients with ACC continued treatment with mitotane during this trail is allowed provided tumor progression on this therapy has been demonstrated under therapeutic plasma level (> 14mg/L) or at maximum individual tolerated dose and mitotane plasma level monitoring is maintained during the trial (mitotane might have been given in the adjuvant and/or established disease settings as long as progression on this therapy before trial inclusion has been documented) For patients with MPP, concurrent therapy with somatostatin, and somatostatin analogues is allowed provided tumor progression on this therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed 5. Patients with ACC with more than three organs involved by disease, combined with unresectable primary tumor. 6. Patients with ACC and uncontrolled hormonal secretion (according to the judgement of the treating physician). 7. Patients with MPP and uncontrolled blood pressure (according to the judgement of the treating physician). 8. Patients with abnormal laboratory values according to the following list (note, lab ranges according to the performing laboratory's reference ranges): a. hemoglobin 1.5 x upper limit of normal (ULN) (note, benign hereditary hyperbilirubinemia, e.g. Gilbert's syndrome is permitted), f. alanine aminotransferase (ALT) > 3 x ULN; if disease metastatic to the liver > 5 x ULN, g. aspartate aminotransferase (AST) > 3 x ULN; if disease metastatic to the liver > 5 x ULN, h. serum creatinine increase (> 1.5 x ULN); however, if creatinine clearance (measured, or calculated according to the Coc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to evaluate safety and tolerability of EO2401 in combination with nivolumab in patients with unresectable, previously treated, and previously untreated, locally advanced or metastatic ACC, and progressive MPP. ;Secondary Objective: The key secondary objectives of the trial: - immunogenicity in relation to T cells of EO2316, EO2317, EO2318, and UCP2 that compose EO2401; T cell cross-reactivity with the human TAAs IL13Ra2, FOXM1, and BIRC5/surviving will also be evaluated. The other secondary objectives of the trial are: - objective response rate (ORR), time to response and duration of response (DOR), and - progression-free survival (PFS) and overall survival (OS). ;Primary end point(s): The primary endpoint regarding safety and tolerability of EO2401 in combination with nivolumab is a descriptive medical assessment of the combined profile of incidences of adverse events (AEs), treatmentemergent AEs (TEAEs), serious AEs (SAEs), deaths, reasons for treatment discontinuation/delays, and laboratory abnormalities using the NCI-CTCAE v5.0 grading system. ;Timepoint(s) of evaluation of this end point: AEs will be monitored throughout the study. AEs are collected from the date of the patient's signing the ICF until 30 days after the final administration of study drug. SAEs with a plausible causal relationship to study drug will be reported from the date of the patient's signing the ICF until indefinitely (regardless of time elapse from the final study drug administration). An AE causally not related to study drug will be monitored (followed-up) until resolution, stabilization, or end of the clinical trial. Clinically relevant laboratory abnormalities will be followed up until they return to normal or become stabilized (permanent condition). Any AE with a plausible causal relationship to study drug as well as all SAEs will be followed up until the event has resolved or stabilized. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoints of the trial are: • Percentage of patients with shown immunogenicity (expansion of specific T cells comparing samples taken at baseline versus on treatment n an individual patient determining if the patient has a positive response to the immunization, or not) in relation to EO2316, EO2317, EO2318, and UCP2 that compose EO2401 by interferon-gamma (IFN-?) enzyme-linked immunospot (ELISpot), and if needed by intracellular cytokines staining, or multimers staining assays. Cross reactivities with the human TAAs IL13Ra2, FOXM1, and BIRC5/survivin will also be evaluated by the same methods. The other secondary endpoints of the trial are: • ORR, time to response and DOR as described by RECIST 1.1 and iRECIST criteria. • PFS as described by RECIST 1.1 and iRECIST criteria, defined as the time interval from the date of first study treatment administration to the date of progression (by RECIST 1.1 or iRECIST criteria) or death due to any cause, whichever is earlier. Patients without progression or death are to be censored at the time of the last tumor assessment. • OS defined as the time interval from the date of first study treatment administration to the date of death due to any cause. Patients alive will be censored at the date of the last documented follow-up. ;Timepoint(s) of evaluation of this end point: • Percentage of patients with shown immunogenicity is evaluated on Week 1, 5 , 7 , 11, 15 and 19, then every 4 weeks of treatment onwards. Post treatment is evaluated on Day 30 and every 8 weeks before disease progression • Objective Response Rate (ORR) and Duration of Response (DOR) as described by RECIST 1.1 and iRECIST criteria • PFS as described by RECIST 1.1 and iRECIST criteria, defined as the time interval from the date of first study treatment administration to the date of progression (by RECIST 1.1 or iRECIST criteria) or death due to any cause, whichever is earlier. Patients without prog | — |
Countries
Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, United States
Contacts
Public ContactJean-Michel Paillarse
ENTEROME
Outcome results
None listed