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Melanoma Stage IVPhase 1/2NCT04455503

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

A Phase 1/2 study testing EVX-02A, EVX-02B and EVX-02A OR EVX-02B in people with Melanoma Stage IV and Melanoma Stage III, run by Evaxion Biotech A/S at 6 sites in Australia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a Phase 1/2, open label, multi-centre study to assess the safety, tolerability, PD, and efficacy of adjuvant immunotherapy EVX-02 vaccine and anti-PD-1 (Nivolumab) in patients who have had a complete resection of a Stage IIIB/IIIC/IIID or Stage IV melanoma who are at high risk of recurrence. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma Stage IV, Melanoma Stage III
What is being tested?
EVX-02A, EVX-02B and EVX-02A OR EVX-02B
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
6 sitesAustralia
Study dates
13 Jul 2020to 28 Mar 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed and dated written ICF prior to performing any protocol-related procedures, which are not part of normal standard care.
  • 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.
  • Male or female ≥ 18 years of age at the time of informed consent.
  • 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:
  • a palpable node (confirmed as malignant by pathology) after the CLND
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  • 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
  • a PET scan positive lymph node of any size confirmed by pathology after CLND
  • 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.
  • 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.
  • Specimen from the resected tumour tissue must be provided for evaluation by NGS.
  • ECOG performance status score of 0 or 1.
  • 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:
  • 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)
  • Life expectancy > 6 months at Screening.
  • 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.
  • 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.
  • 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.
  • 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.
  • Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing.
  • Disease-free at study enrolment (after surgery) based upon pathology report review by the Investigator.

Who cannot join

  • Known or active other malignancies that have needed treatment (excluding palliative radiation) within 2 years prior to Cycle 1 Day 1 are excluded except for the following:
  • Curatively resected non-melanomatous skin cancer
  • Curatively treated cervical carcinoma in situ
  • Non-metastatic breast and prostate cancer patients with stable disease > 12 months
  • Other stable malignancies may be permitted based on case-by-case discussions with Sponsor and Medical Monitor approval.
  • Patients with clinically occult lymph nodes (i.e. detected by SLN biopsy) stage N1a and N2a.
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  • Participated in any other investigational study, unless treatment in that study has been discontinued at least 30 days or period of five half-lives prior to Screening.
  • Known or suspected allergy or hypersensitivity to any of the therapeutic agents to be administered during the study.
  • Uncontrolled concurrent illness including, but not limited to, active infection, symptomatic congestive heart failure or cardiac arrhythmia.
  • Has a history of clinically significant GI disease, renal, hepatic, neurologic, haematologic, endocrine, oncologic, pulmonary, immunologic, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardise the safety of the patient or impact the validity of the study results.
  • Uncontrolled mental disease or psychotic manifestation that, in the opinion of the Investigator, would prohibit compliance with the protocol, the understanding of the ICF, or the ability to withdraw from the study.
  • Known history of or positive test for HIV or known immunodeficiency syndrome (AIDS).
  • For patients with evidence of chronic HBV infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of HCV infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Pregnant or nursing women.
  • Ocular or uveal melanoma.
  • History of carcinomatosis meningitis.
  • History of Grade ≥ 3 allergy to human monoclonal antibodies.
  • 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.
  • 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).
  • Prior investigational melanoma-directed cancer vaccine therapy.
  • Prior chemotherapy, including targeted therapy such as BRAF or MEK inhibition.
  • Use of a non-oncology vaccine therapy for prevention of infectious diseases up to 4 weeks prior to enrolment in the study.
  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Australia6 sites

  • Flinders Medical Centre

    Adelaide, South Australia, 5042

  • Monash Medical Centre

    Clayton, Victoria, 3168

  • Ballarat Health Services

    Drummond, Victoria, 3350

  • Liverpool Hospital

    Goulburn, New South Wales, 2170

  • Peter Maccallum Cancer Centre

    Melbourne, Victoria, 3000

  • Linear Cancer Trials

    Nedlands, Western Australia, 6009

Other trials in Australia

About this study

Official title: A 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

This is a Phase 1/2, open label, multi-centre study to assess the safety, tolerability, PD, and efficacy of adjuvant immunotherapy EVX-02 vaccine and anti-PD-1 (Nivolumab) in patients who have had a complete resection of a Stage IIIB/IIIC/IIID or Stage IV melanoma who are at high risk of recurrence.

Read the detailed description

This study will be conducted in two parts: a safety, efficacy and PD response part using two different drug delivery methods and an expansion cohort.

All patients will be administered with anti-PD-1 once every 4 weeks for up to 1 year commencing on Day 1 and with EVX-02 vaccine as soon as it is produced.

Part 1 will consist of two cohorts:

Cohort A: Will receive EVX- 02A delivered by delivery methodology 1. Cohort B: Will receive EVX- 02B delivered by delivery device 2. Part 2 (Cohort C) will be an expansion cohort. In this part, only one delivery methods, either EVX-02A or EVX-02B with will be used.

Being tested
EVX-02A, EVX-02B, EVX-02A OR EVX-02B
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EVX-02ADrug

    Also called A

    Up to 8 patients will receive EVX-02A administered IM.

  • EVX-02BDrug

    Also called B

    Up to 8 patients will receive EVX-02B administered IM.

  • EVX-02A OR EVX-02BDrug

    Also called C

    EVX-02A or EVX-02B will be used. Patients: 24 to 30

Study groups in NCT04455503
Study groupRoleWhat they receive
Cohort A: Nivolumab and EVX-02AExperimentalEVX-02A administered IM.
Receives: Drug: EVX-02A
Cohort B: Nivolumab and EVX-02BExperimentalEVX-02B administered IM.
Receives: Drug: EVX-02B
Cohort C: Nivolumab and EVX-02A OR Nivolumab and EVX-02BExperimentalThe selected delivery methodology either EVX02A or EVX-02B.
Receives: Drug: EVX-02A OR EVX-02B

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability (Incidence of Treatment-Emergent Adverse Events)

    Measure through CTCAE version 5.0

    Measured: Measurements at Baseline through study completion, an average of 1 year

  2. Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- blood pressure

    Measured by result of the Vital Sign- blood pressure

    Measured: Measurements at Baseline through study completion, an average of 1 year

  3. Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate

    Measured by result of the Vital Sign- heart rate

    Measured: Measurements at Baseline through study completion, an average of 1 year

  4. Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) measure through Physical exam

    Measured by result of the physical exam which includes general appearance, skin, eyes/ears/nose/throat, head and neck.

    Measured: Measurements at Baseline through study completion, an average of 1 year

  5. Pharmacodynamic response (PD) of EVX-02 assessed by IFN-y ELISPOT

    The pharmacodynamic (PD) response of EVX-02 will be assessed by detecting vaccine induced circulating neoepitope-specific T cells. Blood samples will be collected prior, during and after immunization and the immunotherapy induced T cell responses will be assayed by IFN-y ELISPOT.

    Measured: Measurements at Baseline through study completion, an average of 1 year

  6. Pharmacodynamic response (PD) of EVX-02 assessed by MHC I multimer analysis

    The pharmacodynamic (PD) response of EVX-02 will be assessed by detecting vaccine induced circulating neoepitope-specific T cells. Blood samples will be collected prior, during and after immunization. The samples will be analyzed by MHC I multimer analyses detecting neoepitope-recognizing CD8+ T cells reported as frequencies of positive cell out of CD8+ T cells.

    Measured: Measurements at Baseline through study completion, an average of 1 year

  7. Pharmacodynamic response (PD) of EVX-02 by intracellular cytokine staining and flow cytometry

    The pharmacodynamic (PD) response of EVX-02 will be assessed by detecting vaccine induced circulating neoepitpe-specific T cells. Blood samples will be collected prior, during and after immunization. The samples will be analysed by flow cytometry to detect vaccine induced intracellular cytokine response, reported as frequencies of neoepitope-reactive CD4+ cells and CD8+ T cells.

    Measured: Measurements at Baseline through study completion, an average of 1 year

Secondary outcomes (1)

  1. Efficacy measure through Relapse-free survival (RFS)

    Measured by result of Relapse-free survival (RFS)

    Measured: Measurements at Baseline through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2020
  2. Study start13 Jul 2020
  3. Primary completion28 Feb 2023
  4. Study completion28 Mar 2023

Why it stopped: Based on the promising interim results of study part 1, it was decided to further accelerate the development of the 2nd generation DNA plasmid immunotherapy. Therefore enrolment of patients was completed after study part 1

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04455503
Sponsor's protocol ID
EVX-02-001
Status last verified
Feb 2024
First submitted
14 Jun 2020
Last updated
21 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing EVX-02A, EVX-02B and EVX-02A OR EVX-02B in people with Melanoma Stage IV and Melanoma Stage III, run by Evaxion Biotech A/S at 6 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Based on the promising interim results of study part 1, it was decided to further accelerate the development of the 2nd generation DNA plasmid immunotherapy. Therefore enrolment of patients was completed after study part 1). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) (time frame: Measurements at Baseline through study completion, an average of 1 year). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04455503.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2024.

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