Study of Adjuvant Immunotherapy With EVX-02 and Anti-PD-1

Inclusion Criteria

• •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.
• •11. Pregnant or nursing women.
• •12. Ocular or uveal melanoma.
• •13. History of carcinomatosis meningitis.
• •14. History of Grade ≥ 3 allergy to human monoclonal antibodies.
• •15. Active, known, or suspected autoimmune disease or immunosuppressive conditions with the exception of vitiligo, type 1 diabetes, residual autoimmune-related hypothyroidism requiring hormone replacement, or psoriasis not requiring systemic treatment.
• •16. Prior treatment with immune-modulatory agents including, but not limited to: IL-2, CTLA-4 blockade, PD-1/PD-L1 blockade, CD40 stimulation, CD137 stimulation - with the exception of IFN-α given as adjuvant treatment for high risk, surgically resected melanoma (Note. IFN-α therapy must have been discontinued more than 4 weeks prior to enrolment in the study).
• •17. Prior investigational melanoma-directed cancer vaccine therapy.
• •18. Prior chemotherapy, including targeted therapy such as BRAF or MEK inhibition.
• •19. Use of a non-oncology vaccine therapy for prevention of infectious diseases up to 4 weeks prior to enrolment in the study.
• •20. Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to first dose of anti-PD-1 on Day 1. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.