A Single Arm Trial Evaluating the Efficacy and Safety of EVX-01 in Combination With Pembrolizumab in Adults With Unresectable or Metastatic Melanoma

The purpose of this single arm, multi-national clinical trial in patients with metastatic or unresectable melanoma is to evaluate the BOR and compare it to historical data on patients on anti-PD1 treatment with pembrolizumab alone.

Patients will initiate treatment with pembrolizumab at the start of the trial and receive up to 18 treatment cycles (approximately 2 years). Immunization with the EVX-01 will be initiated at Week 12. In total, 10 doses of EVX-01 will be administered intramuscularly, with 6 doses given two weeks apart and 4 booster doses at later time points.

Eligibility Criteria:
Inclusion Criteria:

* Be at least 18 years of age on day of signing informed consent.
* Histologically confirmed, and not amenable to local therapy, metastatic or unresectable melanoma Stage III or Stage IV, as per AJCC 8th ed. staging system.

  1. Patient may not have a diagnosis of uveal or ocular melanoma.
  2. Patients must be treatment naïve to checkpoint inhibitor (CPI) therapy
  3. Patients must have testing for a BRAF mutation prior to study entry.

Note: Patients with BRAF V600E mutant melanoma may have received prior BRAF inhibitor therapy as first-line systemic therapy and be eligible for this study 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 study as first line treatment if they meet the following additional criteria:

i. LDH \< local ULN, ii. No clinically significant tumor related symptoms in the judgment of the investigator, and iii. Absence of rapidly progressing metastatic melanoma in the judgment of the investigator

* Have measurable disease per RECIST 1.1 as assessed by the local site investigator within 4 weeks prior to the first visit. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Patients must be willing and able to provide fresh or frozen tumor tissue from an unresectable or metastatic site of disease for neoepitope and biomarker analyses. If a sufficient amount of tumor tissue from an unresectable or metastatic site is not available prior to the start of the screening phase, subjects must consent to allow the acquisition of additional tumor tissue. In addition, participants may provide additional biopsy at the time of discontinuation due to progression.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

* 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 anti-cancer therapy including investigational agents within 4 weeks prior to treatment.
* Has received prior radiotherapy within 2 weeks of start of study treatment. Participants 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 study intervention. Note: Administration of killed vaccines are allowed.