A single arm trial evaluating the efficacy and safety of EVX-01 in combination with pembrolizumab in adults with unresectable or metastatic melanoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Evaxion A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Mar 2023 → 23 Sep 2025

Decision date (initial)

2024-06-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Evaxion Biotech A/S

External identifiers

EU CT number

2024-512393-10-00

EudraCT number

2022-000899-19

WHO UTN

U1111-1272-6176

ClinicalTrials.gov

NCT05309421

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Pharmacokinetic

To evaluate if EVX-01 improves the best overall response (BOR) in patients with an initial assessment of stable disease (SD) or partial response (PR) after initiating pembrolizumab treatment, as compared to historical outcomes with pembrolizumab alone in metastatic or unresectable melanoma

Secondary objectives 6

1. To evaluate if EVX-01 in combination with pembrolizumab improves the overall response rate, as compared to historical outcomes with pembrolizumab alone in metastatic or unresectable melanoma
2. To evaluate if EVX-01 improves the progression free survival (PFS) in patients with an initial assessment of SD or PR after initiating pembrolizumab treatment, as compared to historical outcomes with pembrolizumab alone in metastatic or unresectable melanoma
3. To evaluate if EVX-01 in combination with pembrolizumab improves the overall survival (OS), as compared to historical outcomes with pembrolizumab alone in metastatic or unresectable melanoma
4. To evaluate the safety of EVX-01 in patients with metastatic or unresectable melanoma on pembrolizumab treatment
5. To evaluate the immunologic response induced by EVX-01
6. To evaluate the feasibility of manufacturing EVX-01

Conditions and MedDRA coding

unresectable or metastatic melanoma

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Danish Medicines Agency, Paul-Ehrlich-Institut, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. The patient (or legally acceptable representative if applicable) provides written informed consent for the trial.
2. Be 18 years of age on day of signing informed consent.
3. Histologically confirmed, and not amenable to local therapy, metastatic or unresectable melanoma Stage III or Stage IV, as per AJCC 8th ed. staging system. a. Patient may not have a diagnosis of uveal or ocular melanoma. b. Patients must be treatment naïve to checkpoint inhibitor (CPI) therapy c. Patients must have a sample taken for testing for a BRAF mutation prior to trial entry.* Patients with BRAF V600E mutant melanoma may have received prior BRAF inhibitor therapy as first-line systemic therapy and be eligible for this trial 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 trial as first-line treatment if they meet the following additional criteria: i. LDH < local ULN at screening ii. No clinically significant tumor related symptoms in the judgment of the investigator iii. Absence of rapidly progressing metastatic melanoma in the judgment of the investigator *It is not a requirement to have the result of the BRAF mutation test available prior to initiating treatment (trial entry); if the result is not known at the time of trial entry, a subject is eligible if the following 3 criteria 3. ci, 3. cii, 3. ciii as above are met at screening irrespective of BRAF mutation status. Historical BRAF testing results (up to 3 years old) is allowed.
4. Have measurable disease per RECIST 1.1 as assessed by the local site investigator within 4 weeks prior to trial allocation. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
5. Patients must be willing and able to provide fresh tumor tissue from an unresectable or metastatic site of disease for neoepitope and biomarker analyses.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 4 weeks prior to trial allocation.
7. A male patient must agree to use contraception and refrain from sperm donation during the treatment period and for at least 120 days after the last dose of trial treatment. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
8. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) b. A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of trial treatment. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. Absence of any condition hampering compliance with the trial protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
10. Have adequate organ function . Specimens must be collected within 10 days prior to trial allocation.
11. Human immunodeficiency virus (HIV) infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as: a. Patients on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening b. Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to trial allocation c. Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to trial allocation
12. Patients who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to trial allocation.
13. Patients with history of HCV infection are eligible if HCV viral load is undetectable at screening.

Exclusion criteria 17

1. A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to first dose of trial treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. 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).
3. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to first dose of trial treatment.
4. Has received prior radiotherapy within 2 weeks prior to first dose of trial treatment. Patients 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.
5. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention.
6. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
7. Has had an allogeneic tissue/solid organ transplant.
8. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
9. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years prior to trial allocation.
10. Known CNS metastases and/or carcinomatous meningitis.
11. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
12. Has an active autoimmune disease that has required systemic treatment in past 2 years prior to trial allocation (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
13. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
14. Has an active infection requiring systemic therapy.
15. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
17. Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite of a BOR of CR or PR for patients with SD at the time of EVX-01 administration and a BOR of CR for patients with PR at the time of EVX-01 administration, during 24 months of treatment with pembrolizumab, as per RECIST 1.1 criteria.

Secondary endpoints 5

1. Overall response rate, defined as the proportion of the patients in the analysis population who have best response as CR or PR assessed 24 months after initiation of treatment with pembrolizumab as per RECIST 1.1 criteria
2. PFS assessed 24 months after initiation of treatment with pembrolizumab and defined as the time from initiation of pembrolizumab treatment to the first documented disease progression per RECIST 1.1. criteria or death due to any causes, whichever occurs first
3. OS, assessed 24 months after initiation of treatment with pembrolizumab and defined as the time from initiation of treatment of pembrolizumab to death due to any cause
4. Number, type and severity of AEs and SAEs
5. Level of immunologic response toward EVX-01 measured by CD4+ and CD8+ neoepitope specific lymphocytes, assessed throughout dosing with EVX-01

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Evaxion A/S

Sponsor organisation

Evaxion A/S

Address

Dr Neergaards Vej 5f

City

Hoersholm

Postcode

2970

Country

Denmark

Scientific contact point

Organisation

Evaxion A/S

Contact name

Stine Friis Thorsen

Public contact point

Organisation

Evaxion A/S

Contact name

Stine Friis Thorsen

Third parties 4

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications