Skipping full lymph node removal for stage III melanoma patients who show a strong response in the index node

OMIT Trial: Omitting Therapeutic Lymph Node Dissection in Patients With Stage IIIB/C Melanoma and Major Pathological Response in the Index Lymph Node After Neoadjudvant Immunotherapy

This trial will see if patients with resectable stage III melanoma who get neoadjuvant ipilimumab plus nivolumab and show a major pathological response in the index lymph node can safely avoid therapeutic lymph node dissection.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 213 (estimated)
• Ages: 16 Years and up
• Sex: All
• Sponsor: Erasmus Medical Center (other)
• Drugs / interventions: ipilimumab, nivolumab, immunotherapy
• Locations: 1 site (Rotterdam, South Holland)
• Trial ID: NCT06754904 on ClinicalTrials.gov

What this trial studies

Patients with macroscopic resectable stage III cutaneous melanoma receive neoadjuvant ipilimumab and nivolumab and have an index lymph node (ILN) marked and sampled to determine pathological response. If the ILN shows a major pathological response (≤10% viable tumor), the protocol omits the planned therapeutic lymph node dissection (TLND) and patients are followed closely for recurrence, distant metastasis, and quality of life. The study builds on prior neoadjuvant trials that linked ILN response to excellent short-term distant metastasis-free and recurrence-free outcomes. Outcomes of interest include event-free survival, distant metastasis-free survival, recurrence-free survival, and treatment-related morbidity and health-related quality of life.

Who should consider this trial

Good fit: Adults (≥16 years) with histologically confirmed macroscopic resectable stage III cutaneous melanoma who are eligible for neoadjuvant ipilimumab plus nivolumab and in whom index lymph node marking is feasible and who can give informed consent.

Not a fit: Patients who do not achieve a major pathological response in the index node, those with non-cutaneous melanoma subtypes (uveal/mucosal), poor performance status, or only in-transit metastases are unlikely to avoid TLND or benefit from the omission strategy.

Why it matters

Potential benefit: If successful, patients could avoid a morbid lymph node dissection, preserving quality of life and reducing surgical complications and costs without increasing recurrence risk.

How similar studies have performed: Previous neoadjuvant trials (NADINA, PRADO) showed improved event-free survival with ipilimumab plus nivolumab and excellent short-term distant metastasis-free and recurrence-free outcomes in patients with major pathological responses, supporting this omission approach.

Eligibility criteria

Inclusion Criteria:

* Patients must be eligible for neoadjuvant treatment (ipilimumab and nivolumab)
* Patients must be 16 years of age or older.
* Patients must have a histologically confirmed diagnosis of macroscopic resectable stage III melanoma (stage III B/C/D) with one or more macroscopic lymph node metastase defined as either one:
* a palpable node, confirmed as melanoma by pathology; a non-palpable but enlarged lymph node according to RECISTv1.1 (at least 15 mm in short axis), confirmed as melanoma by pathology;
* a PET scan positive lymph node of any size confirmed as melanoma by pathology;
* The patient must have a measurable tumor burden that qualifies (according to clinical practice) for neoadjuvant therapy with immune checkpoint inhibitors
* Patients in whom ILN marking is feasible
* Written informed consent

Exclusion Criteria:

* Uveal/ocular or mucosal melanoma
* WHO performance status of two or more
* In-transit metastases only (without cytological or histological proven lymph node involvement)
* Prior targeted therapy targeting BRAF and/or MEK for melanoma
* Prior immunotherapy targeting CTLA-4, PD-1 or PD-L1 for melanoma
* Patients with (history of) distant metastasis (stage IV melanoma)

Where this trial is running

Rotterdam, South Holland

• Erasmus MC — Rotterdam, South Holland, Netherlands (RECRUITING)

Study contacts

• Study coordinator: Drik Grünhagen, MD, PhD

Conditions: Melanoma, Skin, Neoadjuvant, Ipilimumab, Nivolumab, Immunotherapy, Index node, Therapeutic lymph node dissection, Omitting