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

NCT04455503 | Terminated Phase 1 DMC

• 1 other identifier: EVX-02-001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 6

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.

Conditions

Melanoma Stage IV; Melanoma Stage III

Outcome Measures

Primary Outcomes (7)

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

  Measure through CTCAE version 5.0

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

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

  Measured by result of the Vital Sign- blood pressure

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

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

  Measured by result of the Vital Sign- heart rate

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

Secondary Outcomes (1)

• Efficacy measure through Relapse-free survival (RFS)

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

Other Outcomes (1)

• PD response of EVX-02 assessed by monitoring the quantity of cfDNA in plasma

  Measured at Screening, Day -84 to Day -1, Day 1, Day 84, Day 168, Day 252, Day 336 and early termination

Study Arms (3)

Cohort A: Nivolumab and EVX-02A

EXPERIMENTAL

EVX-02A administered IM.

Drug: EVX-02A

Cohort B: Nivolumab and EVX-02B

EXPERIMENTAL

EVX-02B administered IM.

Drug: EVX-02B

Cohort C: Nivolumab and EVX-02A OR Nivolumab and EVX-02B

EXPERIMENTAL

The selected delivery methodology either EVX02A or EVX-02B.

Drug: EVX-02A OR EVX-02B

Interventions

EVX-02A DRUG

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

Also known as: A

Cohort A: Nivolumab and EVX-02A

EVX-02B DRUG

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

Also known as: B

Cohort B: Nivolumab and EVX-02B

EVX-02A OR EVX-02B DRUG

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

Also known as: C

Cohort C: Nivolumab and EVX-02A OR Nivolumab and EVX-02B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:
• 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)
• Life expectancy \> 6 months at Screening.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Evaxion Biotech A/S: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (6)

Liverpool Hospital

Goulburn, New South Wales, 2170, Australia

Location

Flinders Medical Centre

Adelaide, South Australia, 5042, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Ballarat Health Services

Drummond, Victoria, 3350, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Linear Cancer Trials

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Dr Bavanthi Balakrishnar

  Liverpool Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2020
• First Posted: July 2, 2020
• Study Start: July 13, 2020
• Primary Completion: February 28, 2023
• Study Completion: March 28, 2023
• Last Updated: February 21, 2024

Record last verified: 2024-02

Locations

AU (6)