One-dose pembrolizumab before surgery for high-risk localized melanoma

A Phase 2 Clinical Trial on Neoadjuvant Pembrolizumab in Patients Diagnosed With High-risk Melanoma Without Clinical Evidence of Metastatic Dissemination.

This trial gives one dose of pembrolizumab six weeks before surgery to see if it helps adults with high‑risk melanoma that appears confined on scans.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Universitair Ziekenhuis Brussel (other)
• Drugs / interventions: pembrolizumab, immunotherapy
• Locations: 1 site (Jette, Brussels Capital)
• Trial ID: NCT07448831 on ClinicalTrials.gov

What this trial studies

The NeoSenti trial enrolls adults with high‑risk primary cutaneous melanoma and no evidence of distant spread. Eligible participants receive a single infusion of pembrolizumab about six weeks before their planned sentinel lymph node biopsy and wide local excision. Surgical findings determine whether patients continue with standard adjuvant immunotherapy for one year or enter routine follow‑up, and all participants are followed with scans, blood tests, and check‑ups for five years. The study also uses baseline imaging, lymph node ultrasound, and sometimes a Merlin™ risk test to refine eligibility and risk stratification.

Who should consider this trial

Good fit: Adults (≥18) with high‑risk primary cutaneous melanoma (pT3b‑4b or pT1b‑3a with Merlin™ high risk), no evidence of metastatic disease on PET/CT and ultrasound, amenable to sentinel lymph node biopsy, ECOG 0–2, no prior systemic melanoma therapy, and adequate organ function.

Not a fit: Patients with known distant metastatic disease, prior systemic treatment for melanoma, low‑risk tumors, or medical conditions that prevent safe use of immunotherapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, giving pembrolizumab before surgery could reduce microscopic lymph node spread and improve long‑term outcomes for people with high‑risk melanoma.

How similar studies have performed: Neoadjuvant PD‑1 blockade in melanoma has produced promising pathological responses in prior studies, but single‑dose preoperative approaches remain relatively novel and need confirmation in trials.

Eligibility criteria

Inclusion Criteria:

≥ 18 years of age on the day of signing the informed consent.

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

Amendable to sentinel lymph node biopsy.

No evidence of metastatic dissemination as demonstrated by PET/CT, ultrasound of the draining lymph node basin, and clinical examination.

No prior exposure to systemic treatment for melanoma (adjuvant or curative).

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.

Adequate baseline organ function as defined by local institutional standards.

Women:

* Female patients must be surgically sterile or be postmenopausal (A postmenopausal state is defined as no menses for 12 months without an alternative medical cause).
* If a female patient is a woman of childbearing potential (WOCBP) they must agree to use highly effective contraception measures during the period of therapy, which should be continued for at least 4 months following the last dose of pembrolizumab as indicated in the SmPC. A list of highly effective contraceptive measures is included in appendix 1 All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment and pregnancy testing should be conducted within 24h prior to the first dose of immune checkpoint inhibitors and thereafter monthly until 4 months following the last dose study treatment.
* Should not be breastfeeding at screening or during study treatment.

Men with a female partner of childbearing potential must agree to use highly 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.

Capable of providing documented informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

Patients with uveal melanoma, mucosal melanoma and melanoma of unknown primary origin.

Active autoimmune disease requiring systemic treatment.

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.

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.

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.

Active infection at the time of screening (e.g. wound infection).

Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatment, or excipients.

History of organ allograft.

Patients who have previously been exposed to checkpoint inhibitors.

Prior transplantation of human cells, tissues and organs (e.g. liver transplant) or candidates for any type of transplantation.

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.

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Any contra-indication for evaluation by whole body 18F-FDG-PET/CT or MRI.

Where this trial is running

Jette, Brussels Capital

• UZ Brussel — Jette, Brussels Capital, Belgium (RECRUITING)

Study contacts

• Principal investigator: Bart Neyns, Prof, MD, PhD — Universitair Ziekenhuis Brussel

Conditions: Melanoma