A Phase 1/2, Study of Adjuvant Immunotherapy With EVX-02 and Anti-PD-1 After Complete Resection of Stage IIIB/IIIC/IIID or Stage IV Melanoma in Patients at High Risk for Recurrence
Overview
- Phase
- Phase 1
- Intervention
- EVX-02A
- Conditions
- Melanoma Stage IV
- Sponsor
- Evaxion Biotech A/S
- Enrollment
- 15
- Locations
- 6
- Primary Endpoint
- Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Phase 1/2, open label, multi-centre study to assess the safety, tolerability, PD, and efficacy of adjuvant immunotherapy EVX-02 vaccine and anti-PD-1 (Nivolumab) in patients who have had a complete resection of a Stage IIIB/IIIC/IIID or Stage IV melanoma who are at high risk of recurrence.
Detailed Description
This study will be conducted in two parts: a safety, efficacy and PD response part using two different drug delivery methods and an expansion cohort. All patients will be administered with anti-PD-1 once every 4 weeks for up to 1 year commencing on Day 1 and with EVX-02 vaccine as soon as it is produced. Part 1 will consist of two cohorts: Cohort A: Will receive EVX- 02A delivered by delivery methodology 1. Cohort B: Will receive EVX- 02B delivered by delivery device 2. Part 2 (Cohort C) will be an expansion cohort. In this part, only one delivery methods, either EVX-02A or EVX-02B with will be used.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed and dated written ICF prior to performing any protocol-related procedures, which are not part of normal standard care.
- •Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumour sample including core needle biopsy as required, and other requirements of the study.
- •Male or female ≥ 18 years of age at the time of informed consent.
- •Stage IIIB/IIIC/IIID or Stage IV AJCC (8th edition) (AJCC, 2018) before complete resection.
- •Please note: If Stage III melanoma (whether Stage IIIB or IIIC or IIID) the patients must have clinically detectable lymph nodes that are confirmed as malignant on the pathology report and/or ulcerated primary lesions, and/or in transit metastasis. The pathology report must be reviewed, signed and dated by the Investigator; this process must be done prior to enrolling patients into the study. Clinically detectable lymph nodes are defined as:
- •a palpable node (confirmed as malignant by pathology) after the CLND
- •a non-palpable but enlarged lymph node by CT scan (at least 15 mm in short axis) and confirmed as malignant by pathology after the CLND
- •a PET scan positive lymph node of any size confirmed by pathology after CLND
- •evidence of pathologically macro metastatic disease in one or more lymph nodes defined by one or more foci of melanoma at least 1 cm in diameter If Stage IV melanoma, the pathology report confirming negative margins must be reviewed, dated, and signed by the Investigator prior to randomisation.
- •Cutaneous Melanoma, with metastases to regional lymph nodes or distant metastases, or in transit metastases, that can be surgically resected with negative margin on resected specimens.
Exclusion Criteria
- •Known or active other malignancies that have needed treatment (excluding palliative radiation) within 2 years prior to Cycle 1 Day 1 are excluded except for the following:
- •Curatively resected non-melanomatous skin cancer
- •Curatively treated cervical carcinoma in situ
- •Non-metastatic breast and prostate cancer patients with stable disease \> 12 months
- •Other stable malignancies may be permitted based on case-by-case discussions with Sponsor and Medical Monitor approval.
- •Patients with clinically occult lymph nodes (i.e. detected by SLN biopsy) stage N1a and N2a.
- •Participated in any other investigational study, unless treatment in that study has been discontinued at least 30 days or period of five half-lives prior to Screening.
- •Known or suspected allergy or hypersensitivity to any of the therapeutic agents to be administered during the study.
- •Uncontrolled concurrent illness including, but not limited to, active infection, symptomatic congestive heart failure or cardiac arrhythmia.
- •Has a history of clinically significant GI disease, renal, hepatic, neurologic, haematologic, endocrine, oncologic, pulmonary, immunologic, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardise the safety of the patient or impact the validity of the study results.
Arms & Interventions
Cohort A: Nivolumab and EVX-02A
EVX-02A administered IM.
Intervention: EVX-02A
Cohort B: Nivolumab and EVX-02B
EVX-02B administered IM.
Intervention: EVX-02B
Cohort C: Nivolumab and EVX-02A OR Nivolumab and EVX-02B
The selected delivery methodology either EVX02A or EVX-02B.
Intervention: EVX-02A OR EVX-02B
Outcomes
Primary Outcomes
Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate
Time Frame: Measurements at Baseline through study completion, an average of 1 year
Measured by result of the Vital Sign- heart rate
Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) measure through Physical exam
Time Frame: Measurements at Baseline through study completion, an average of 1 year
Measured by result of the physical exam which includes general appearance, skin, eyes/ears/nose/throat, head and neck.
Safety and tolerability (Incidence of Treatment-Emergent Adverse Events)
Time Frame: Measurements at Baseline through study completion, an average of 1 year
Measure through CTCAE version 5.0
Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- blood pressure
Time Frame: Measurements at Baseline through study completion, an average of 1 year
Measured by result of the Vital Sign- blood pressure
Pharmacodynamic response (PD) of EVX-02 assessed by IFN-y ELISPOT
Time Frame: Measurements at Baseline through study completion, an average of 1 year
The pharmacodynamic (PD) response of EVX-02 will be assessed by detecting vaccine induced circulating neoepitope-specific T cells. Blood samples will be collected prior, during and after immunization and the immunotherapy induced T cell responses will be assayed by IFN-y ELISPOT.
Pharmacodynamic response (PD) of EVX-02 assessed by MHC I multimer analysis
Time Frame: Measurements at Baseline through study completion, an average of 1 year
The pharmacodynamic (PD) response of EVX-02 will be assessed by detecting vaccine induced circulating neoepitope-specific T cells. Blood samples will be collected prior, during and after immunization. The samples will be analyzed by MHC I multimer analyses detecting neoepitope-recognizing CD8+ T cells reported as frequencies of positive cell out of CD8+ T cells.
Pharmacodynamic response (PD) of EVX-02 by intracellular cytokine staining and flow cytometry
Time Frame: Measurements at Baseline through study completion, an average of 1 year
The pharmacodynamic (PD) response of EVX-02 will be assessed by detecting vaccine induced circulating neoepitpe-specific T cells. Blood samples will be collected prior, during and after immunization. The samples will be analysed by flow cytometry to detect vaccine induced intracellular cytokine response, reported as frequencies of neoepitope-reactive CD4+ cells and CD8+ T cells.
Secondary Outcomes
- Efficacy measure through Relapse-free survival (RFS)(Measurements at Baseline through study completion, an average of 1 year)