adrenal cancer
Conditions
Interventions
Cohort 1
Priming Phase
Injection of 1 ml of EO2401 every 2 weeks. EO2401 injections will be given 4
times in total during this phase. An intravenous infusion of nivolumab will be
given 3 hours after
Sponsors
Enterome
Eligibility
Age
18 Years to 99 Years
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), and should within these lines of therapy for advanced/metastatic disease, or as neoadjuvant/adjuvant therapy, have received mitotane therapy delivered at an adequate dose 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, neoadjuvant/adjuvant therapy (including mitotane with or without chemotherapy) for patients after complete responses 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 neoadjuvant/adjuvant therapy, or therapy for advanced/metastatic disease can continue mitotane during study therapy provided definitions regarding eligibility of continued mitotane therapy are fulfilled 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. 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 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 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
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 β-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 patient is eligible (see section 6.9.2). 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 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 according to the following list (note, lab ranges according to the performing laboratory's reference ranges): a. lymphocyte count decreased, grade 2 (lymphocytes 1.5 x upper limit of normal (ULN), g. alanine aminotransferase (ALT) > 3 x ULN; if disease metastatic to the liver > 5 x ULN, h. aspartate aminotransferase
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the phase 1 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. The primary objective of the phase 2 part of this trial is to determine the effect of EO2401/nivolumab on the progression-free survival rate at 6 months, per investigator/local site assessments, for patients treated in the randomized extension of Cohort 2A* (patients treated with EO2401 monotherapy and nivolumab monotherapy, respectively, will constitute internal concurrent controls in the randomized extension). * Cohort 2A = patients with ACC who had prior systemic therapy for established locally advanced or metastatic disease | — |
Secondary
| Measure | Time frame |
|---|---|
| The key secondary endpoints of the trial are: • Percentage of patients with shown immunogenicity in relation to EO2316, EO2317, EO2318, and UCP2 that compose EO2401 The other secondary endpoints of the trial are: • Objective response rate, time to response and Duration of response as described by RECIST 1.1 and iRECIST criteria. • Progression-free survival 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. • Overall survival 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. • In addition, in the randomized extension of Cohort 2A safety and tolerability of EO2401/nivolumab assessed versus internal concurrent controls | — |
Countries
Netherlands
Outcome results
None listed