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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04455503




Registration number
NCT04455503
Ethics application status
Date submitted
14/06/2020
Date registered
2/07/2020
Date last updated
10/03/2021

Titles & IDs
Public title
Study of Adjuvant Immunotherapy With EVX-02 and Anti-PD-1
Scientific 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
Secondary ID [1] 0 0
EVX-02-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma Stage IV 0 0
Melanoma Stage III 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EVX-02A
Treatment: Drugs - EVX-02B
Treatment: Drugs - EVX-02A OR EVX-02B

Experimental: Cohort A: Nivolumab and EVX-02A - EVX-02A administered IM.

Experimental: Cohort B: Nivolumab and EVX-02B - EVX-02B administered IM.

Experimental: Cohort C: Nivolumab and EVX-02A OR Nivolumab and EVX-02B - The selected delivery methodology either EVX02A or EVX-02B.


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

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

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) - Measure through CTCAE version 5.0
Timepoint [1] 0 0
Measurements at Baseline through study completion, an average of 1 year
Primary outcome [2] 0 0
Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- blood pressure - Measured by result of the Vital Sign- blood pressure
Timepoint [2] 0 0
Measurements at Baseline through study completion, an average of 1 year
Primary outcome [3] 0 0
Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate - Measured by result of the Vital Sign- heart rate
Timepoint [3] 0 0
Measurements at Baseline through study completion, an average of 1 year
Primary outcome [4] 0 0
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.
Timepoint [4] 0 0
Measurements at Baseline through study completion, an average of 1 year
Primary outcome [5] 0 0
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.
Timepoint [5] 0 0
Measurements at Baseline through study completion, an average of 1 year
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
Measurements at Baseline through study completion, an average of 1 year
Primary outcome [7] 0 0
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.
Timepoint [7] 0 0
Measurements at Baseline through study completion, an average of 1 year
Secondary outcome [1] 0 0
Efficacy measure through Relapse-free survival (RFS) - Measured by result of Relapse-free survival (RFS)
Timepoint [1] 0 0
Measurements at Baseline through study completion, an average of 1 year

Eligibility
Key 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. 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 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of additional malignancies, except:

i. Non-melanoma skin cancer where a complete remission was achieved at least 3 years
prior to Screening; ii. Patients who have been disease-free for at least 5 years and
are deemed by the Investigator to be at low risk for recurrence of that malignancy;
iii. Patients with the following cancers if diagnosed and treated within the past 5
years:

- Cervical cancer in situ;

- BCC;

- SCC of the skin;

- Non-muscle invasive bladder cancer.

2. Patients with clinically occult lymph nodes (i.e. detected by SLN biopsy) stage N1a
and N2a.

3. 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.

4. Known or suspected allergy or hypersensitivity to any of the therapeutic agents to be
administered during the study.

5. Uncontrolled concurrent illness including, but not limited to, active infection,
symptomatic congestive heart failure or cardiac arrhythmia.

6. 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.

7. 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.

8. Known history of or positive test for HIV or known immunodeficiency syndrome (AIDS).

9. For patients with evidence of chronic HBV infection, the HBV viral load must be
undetectable on suppressive therapy, if indicated.

10. 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.

11. Pregnant or nursing women.

12. Ocular or uveal melanoma.

13. History of in transit metastases

14. History of carcinomatosis meningitis.

15. History of Grade = 3 allergy to human monoclonal antibodies.

16. 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.

17. 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-a given as adjuvant treatment for high risk, surgically resected
melanoma (Note. IFN-a therapy must have been discontinued more than 4 weeks prior to
enrolment in the study).

18. Prior investigational melanoma-directed cancer vaccine therapy.

19. Prior chemotherapy, including targeted therapy such as BRAF or MEK inhibition.

20. Use of a non-oncology vaccine therapy for prevention of infectious diseases up to 4
weeks prior to enrolment in the study.

21. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Goulburn
Recruitment hospital [2] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
Ballarat Health Services - Drummond
Recruitment hospital [5] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [6] 0 0
Linear Cancer Trials - Nedlands
Recruitment postcode(s) [1] 0 0
2170 - Goulburn
Recruitment postcode(s) [2] 0 0
5042 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3350 - Drummond
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Evaxion Biotech A/S
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT04455503
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dr Bavanthi Balakrishnar
Address 0 0
Liverpool Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Brit Stenfeldt
Address 0 0
Country 0 0
Phone 0 0
+4531318993
Fax 0 0
Email 0 0
info@evaxion-biotech.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04455503