unresectable or metastatic melanoma
Conditions
Interventions
Product Name: EVX-01
Product Code: [EVX-01]
Pharmaceutical Form: Solution for injection/infusion
Current Sponsor code: EVX-01
Other descriptive name: EVX-01
Concentration unit: µg/ml microgram(s)/mill
Sponsors
Evaxion Biotech A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient (or legally acceptable representative if applicable) provides written informed consent for the trial. 2. Be ³ 18 years of age on day of signing informed consent. 3. Histologically confirmed, and not amenable to local therapy, metastatic or unresectable melanoma Stage III or Stage IV, as per AJCC 8th ed. staging system. a. Patient may not have a diagnosis of uveal or ocular melanoma. b. Patients must be treatment naïve to checkpoint inhibitor (CPI) therapy c. Patients must have testing for a BRAF mutation prior to trial entry. Patients with BRAF V600E mutant melanoma may have received prior BRAF inhibitor therapy as first-line systemic therapy and be eligible for this trial as second line treatment. At the discretion of the investigator, patients with BRAF V600E mutant melanoma who have NOT received a BRAF inhibitor are also eligible for this trial as first-line treatment if they meet the following additional criteria: i. LDH 350 cells/mm3 at time of screening b. Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to trial allocation c. Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to trial alloca
Exclusion criteria
Exclusion criteria: -A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to first dose of trial treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137). -Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to first dose of trial treatment. - Has received prior radiotherapy within 2 weeks prior to first dose of trial treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease. -Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention. -Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment. -Has had an allogeneic tissue/solid organ transplant. -Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. -Has a known additional malignancy that is progressing or has required active treatment within the past 3 years prior to trial allocation. - Known CNS metastases and/or carcinomatous meningitis. - Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients. -Has an active autoimmune disease that has required systemic treatment in past 2 years prior to trial allocation (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. -Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease. - Has an active infection requiring systemic therapy. - HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease. - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator. -Has a known psychiatric or substance abuse disorder that would interfere with the patient’s ability to cooperate with the requirements of the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate if EVX-01 improves the best overall response (BOR) in patients with an initial assessment of stable disease (SD) or partial response (PR) after initiating pembrolizumab treatment, as compared to historical outcomes with pembrolizumab alone in metastatic or unresectable melanoma;Secondary Objective: -To evaluate if EVX-01 in combination with pembrolizumab improves the overall response rate, as compared to historical outcomes with pembrolizumab alone in metastatic or unresectable melanoma -To evaluate if EVX-01 improves the progression free survival (PFS) in patients with an initial assessment of SD or PR after initiating pembrolizumab treatment, as compared to historical outcomes with pembrolizumab alone in metastatic or unresectable melanoma -To evaluate if EVX-01 in combination with pembrolizumab improves the overall survival (OS), as compared to historical outcomes with pembrolizumab alone in metastatic or unresectable melanoma -To evaluate the safety of EVX-01 in patients with metastatic or unresectable melanoma on pembrolizumab treatment -To evaluate the immunologic response induced by EVX-01 -To evaluate the feasibility of manufacturing EVX-01;Primary end point(s): Composite of a BOR of CR or PR for patients with SD at the time of EVX-01 administration and a BOR of CR for patients with PR at the time of EVX-01 administration, during 24 months of treatment with pembrolizumab, as per RECIST 1.1 criteria.;Timepoint(s) of evaluation of this end point: The final analysis on the primary endpoint will be conducted after all patients have either completed the approximately two-year treatment with pembrolizumab or have been censored due to an event before. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Overall response rate, defined as the proportion of the patients in the analysis population who have best response as CR or PR assessed 24 months after initiation of treatment with pembrolizumab as per RECIST 1.1 criteria • PFS assessed 24 months after initiation of treatment with pembrolizumab and defined as the time from initiation of pembrolizumab treatment to the first documented disease progression per RECIST 1.1. criteria or death due to any causes, whichever occurs first • OS, assessed 24 months after initiation of treatment with pembrolizumab and defined as the time from initiation of treatment of pembrolizumab to death due to any cause • Number, type and severity of AEs and SAEs • Level of immunologic response toward EVX-01 measured by CD4+ and CD8+ neoepitope specific lymphocytes, assessed throughout dosing with EVX-01;Timepoint(s) of evaluation of this end point: The final analysis on the sec. endpoint will be conducted after all patients have either completed the approximately two-year treatment with pembrolizumab or have been censored due to an event before. | — |
Countries
Australia, France, Italy, Spain, United States
Contacts
Public ContactAgon Hyseni
EVAXION BIOTECH A/S
Outcome results
None listed