A phase 2 clinical trial on neoadjuvant pembrolizumab in patients diagnosed with high-risk melanoma without clinical evidence of metastatic dissemination.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Brussel

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

11 Apr 2025 → ongoing

Decision date (initial)

2025-03-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Diagnosis

To estimate the antitumor activity of pembrolizumab in high-risk primary cutaneous melanoma population (pT1b to pT4b) without clinical evidence of metastasis (cN0M0) in the neoadjuvant setting.

Secondary objectives 5

1. To estimate relapse-free survival (RFS), distant-metastasis free survival (DMFS), and overall survival (OS) over a period of five years.
2. To document the incidence and severity of adverse events in study patients.
3. To measure health-related quality of life (HRQoL).
4. Explore histopathological hallmarks of pathological response of melanoma micrometastasis in the sentinel node.
5. Explore the relation between the gene expression signature in the primary tumor and resistance to checkpoint inhibition.

Conditions and MedDRA coding

Melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. ≥18 years of age on the day of signing informed consent.
2. Histologically confirmed high risk primary cutaneous pT1b-4b melanoma. High risk primary melanoma is defined in this study as the following AJCC8 T-stages: • pT1b-3a, with a poor prognostic score on the Merlin™ test (“Merlin™ high risk”); • pT3b-4b, irrespective of their Merlin™ test result
3. Amenable to sentinel lymph node biopsy.
4. No evidence of metastatic dissemination as demonstrated by PET/CT, ultrasound of the draining lymph node basin, and clinical examination.
5. No prior exposure to systemic treatment for melanoma.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2 assessed within 7 days prior to the first dose of study treatment.
7. Adequate organ function as defined: Absolute neutrophil count ≥ 1.2 x 103/mm3, Hemoglobin ≥ 9.0 g/dL, Platelet count ≥ 75 x 103/mm3, Total bilirubin ≤ 1.5 x ULN, ALT ≤ 2.5 x ULN, Calculated creatinine clearance ≥ 50 mL/min). Specimens must be collected within 7 days prior to the start of study treatment.
8. Women: a. Not a woman of childbearing potential (WOCBP) b. Women of childbearing potential must have a negative serum pregnancy test during screening and within 72 hours prior to treatment initiation and agree to use effective contraception of their choice throughout the treatment period, and for 16 weeks after the last dose of study treatment. c. Women who are not breastfeeding
9. Men with a female partner of childbearing potential must agree to use effective contraception from 14 days prior to administration of the first dose of study treatment or have either had a prior vasectomy, throughout the treatment period, and for 16 weeks after the last dose of study treatment.
10. Capable of providing documented informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Participants (or legally acceptable representative) must provide documented informed consent

Exclusion criteria 13

1. Patients with uveal melanoma and melanoma of unknown primary origin.
2. Active autoimmune disease requiring systemic treatment
3. Patients with a history of previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 3 years prior to screening and no additional therapy is required or anticipated to be required during the study period.
4. Known Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Exception: subjects with laboratory evidence of cleared HBV and HCV infection will be permitted.
5. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject’s safety, obtaining informed consent, or compliance with study procedures.
6. Active infection at the time of screening (e.g. wound infection)
7. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatment, or excipients
8. History of organ allograft.
9. Patients who have previously been exposed to checkpoint inhibitors
10. Prior transplantation of human cells, tissues and organs (e.g. liver transplant) or candidates for any type of transplantation.
11. 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.
12. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
13. Any contra-indication for evaluation by whole body 18F-FDG-PET/CT or MRI.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The rate of negative sentinel node procedures (=absence of viable melanoma metastases found on histopathological examination of the sentinel node) following the neoadjuvant treatment.

Secondary endpoints 5

1. RFS is defined as the time from study recruitment to the date of first recurrence (or death from any cause), DMFS from recruitment to the first diagnosis of a distant metastasis (or death from any cause) and OS is defined as the time of recruitment until the date of death from any cause.
2. Safety as assessed by anamnesis, clinical examination, analysis of blood and any additional medical examination that is indicated. AE will be graded by the Common Terminology Criteria of Adverse events (CTCAE), version 5.0 (National Institutes of Health, National Cancer Institute).
3. Health-related quality of life through the following patient-reported outcomes measure (PROM): European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30).
4. Describe markers of pathological response of melanoma micrometastasis in the sentinel node.
5. Describe the relation between the gene expression signature in bulk RNA sequencing of the primary tumor and the result of the sentinel node biopsy.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Brussel

Sponsor organisation

UZ Brussel

Address

Laarbeeklaan 101

City

Jette

Postcode

1090

Country

Belgium

Scientific contact point

Organisation

UZ Brussel

Contact name

Datamanagement oncologie

Public contact point

Organisation

UZ Brussel

Contact name

Datamanagement oncologie

Locations

1 EU/EEA country · 1 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 20 files

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

Application history

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