Clinical trial NCT05309421: A Single Arm Trial Evaluating the Efficacy and Safety of EVX-01 in Combination With Pembrolizumab in Adults With Unresectable or Metastatic Melanoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Melanoma Stage III
Melanoma Stage IV
Lead sponsor: Evaxion Biotech A/S
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-04-04
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

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.

Primary outcomes:
measure: Change in the best overall response (BOR)
timeFrame: Measurements at Baseline through study completion (up to 102 weeks)
Secondary outcomes:
measure: Change in overall response rate
timeFrame: Measurements at Baseline through study completion (up to 102 weeks)
measure: Change in progression free survival (PFS)
timeFrame: Measurements at Baseline through study completion (up to 102 weeks)
measure: Change in overall survival (OS)
timeFrame: Measurements at Baseline through study completion (up to 102 weeks)
measure: Number, type and severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Measurements at Baseline through study completion (up to 102 weeks)
measure: Immunologic response induced by EVX-01
timeFrame: Measurements at Baseline through study completion (up to 102 weeks)
measure: Percentage of patients in which EVX-01 is generated, produced, and administered
timeFrame: From tumor biopsy sampling to first dose of EVX-01 (up to 16 weeks)
Other outcomes:
Locations:
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
city: Ballarat Central
country: Australia
facility: Ballarat Health Services (Grampians Health)
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
Study officials:
References:
citation: 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.