EVX-02-001: This phase I/IIb trial is trying to understand whether an adjuvant immunotherapy is safe, tolerable and effective for patients who have had a stage III or stage IV melanoma removed, but are at high risk of it coming backA 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

Inclusion

1. Signed and dated written ICF prior to performing any protocol-related procedures, which are not part of normal standard care.
2. 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.
3. Male or female ≥ 18 years of age at the time of informed consent.

4. 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:

   1. a palpable node (confirmed as malignant by pathology) after the CLND
   2. 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
   3. a PET scan positive lymph node of any size confirmed by pathology after CLND
   4. 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.
5. 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.
6. Specimen from the resected tumour tissue must be provided for evaluation by NGS.
7. ECOG performance status score of 0 or 1.

8. Screening laboratory values must meet the following criteria and must be reconfirmed for eligibility within 72 hours prior to first dose of anti-PD-1 on Day 1:

   i. WBCs ≥ 2000/μL (2.0 x 109/L) ii. Neutrophils ≥ 1500/μL (1.5 x109/L) iii. Platelets ≥ 100 x 10³/μL (100 x 109/L) iv. Haemoglobin ≥ 9.0 g/dL (90 g/L) v. Creatinine Serum creatinine ≤ 1.5 x ULN or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula) vi. AST ≤ 3 x ULN vii. ALT ≤ 3 x ULN viii. Total Bilirubin ≥ 1.5 x ULN (except patients with Gilbert Syndrome who must have total bilirubin < 3.0 mg/dL)

9. Life expectancy > 6 months at Screening.
10. WOCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
11. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of hCG]) within 24 hours prior to first dose of anti-PD-1 on Day 1.
12. WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle). The half-life of nivolumab is up to 25 days. WOCBP should therefore use an adequate method to avoid pregnancy for a total of 23 weeks post-treatment completion.
13. Men who are sexually active with a WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of the study drug(s) plus 90 days (duration of sperm turnover). The half-life of nivolumab is up to 25 days, men should therefore use an adequate method of contraception for a total of 31 weeks post-treatment completion.
14. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing.
15. Disease-free at study enrolment (after surgery) based upon pathology report review by the Investigator.