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

An Open Label, Single Arm Trial Evaluating the Efficacy and Safety of EVX-01 in Combination With Pembrolizumab in Checkpoint Inhibitor Treatment naïve 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Unresectable Melanoma; Melanoma Stage IV
• Intervention / Treatment: Drug: EVX-01; Drug: Pembrolizumab 25 MG/ML

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Wollstonecraft, New South Wales, Australia, 2065
      • Melanoma Institute Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • One Clinical Research
• Italy
  • Milan, Italy
    • Divisione di Oncologia Medica del Melanoma
  • Napoli, Italy
    • Instituto Nazionale Tumori IRCCS Fondazione

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EVX-01 in combination with pembrolizumab; EVX-01 is administered im. Pembrolizumab is administered according to label	Drug: EVX-01; Investigational drug given in combination with standard of care; Drug: Pembrolizumab 25 MG/ML; Standard of care; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the best overall response (BOR)	Composite of a BOR of complete response (CR) or PR for patients with SD at the time of first EVX-01 administration and a BOR of CR for patients with PR at the time of first EVX-01 administration, within 2 years of treatment with pembrolizumab, as per RECIST 1.1 criteria	Measurements at Baseline through study completion (up to 102 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in overall response rate	Overall response rate, defined as the proportion of the patients who have best response as CR or PR assessed 2 years after initiation of treatment with pembrolizumab, as per RECIST 1.1 criteria	Measurements at Baseline through study completion (up to 102 weeks)
Change in progression free survival (PFS)	PFS in patients with an assessment of SD, PR, or CR at the time of first EVX-01 administration, assessed 2 years after initiation of treatment with pembrolizumab and defined as the time from the first EVX-01 administration to the first documented disease progression per RECIST 1.1. criteria or death due to any causes, whichever occurs first	Measurements at Baseline through study completion (up to 102 weeks)
Change in overall survival (OS)	OS assessed 2 years after initiation of treatment with pembrolizumab and defined as the time from initiation of treatment of pembrolizumab to death due to any cause	Measurements at Baseline through study completion (up to 102 weeks)
Number, type and severity of adverse events (AEs) and serious adverse events (SAEs)	Number, type and severity of adverse events (AEs) and serious adverse events (SAEs)	Measurements at Baseline through study completion (up to 102 weeks)
Immunologic response induced by EVX-01	Activation and level of neoepitope specific T-cells before, during and after EVX-01 immunization	Measurements at Baseline through study completion (up to 102 weeks)
Percentage of patients in which EVX-01 is generated, produced, and administered	Percentage of patients in which EVX-01 is generated, produced, and administered	From tumor biopsy sampling to first dose of EVX-01 (up to 16 weeks)

Collaborators and Investigators

• Sponsor: Evaxion Biotech A/S
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Long GV, Ferrucci PF, Khattak A, Meniawy TM, Ott PA, Chisamore M, Trolle T, Hyseni A, Heegaard E. KEYNOTE - D36: personalized immunotherapy with a neoepitope vaccine, EVX-01 and pembrolizumab in advanced melanoma. Future Oncol. 2022 Oct;18(31):3473-3480. doi: 10.2217/fon-2022-0694. Epub 2022 Sep 1.

Helpful Links

• PR

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2022
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: March 22, 2022
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: cancer vaccine; Personalized immunotherapy; Personal cancer vaccine; EVX-01
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; pembrolizumab
• Other Study ID Numbers: EVX-01-001; KEYNOTE-D36 (Other Identifier: Merck Sharp & Dohme Corp.); 2024-512393-10-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No