A Phase 2 Clinical Trial of Neoadjuvant Relatlimab and Nivolumab in High Risk, Clinical Stage II Cutaneous Melanoma

NCT05418972 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: MIA2022/CT/432, CA224-137
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant therapy is feasible in stage II melanoma, and the dual inhibition of the distinct LAG-3 and PD-1 checkpoint pathways with relatlimab and nivolumab has a synergistic effect in the tumour microenvironment leading to a pathological response after 2 doses of therapy.

Conditions

Stage II Melanoma

Keywords

Neoadjuvant; Nivolumab; Relatlimab; Pathological response; Biomarkers; Feasibility; Sentinel node biopsy; Lymphoscintigraphy; Single-photon emission computed tomography (SPECT)

Outcome Measures

Primary Outcomes (2)

• Pathological response rate

  The primary endpoint is the pathological response rate at surgery (between days 43 and 56) from the first dose of neoadjuvant study treatment. The pathological response is categorised thus: * Complete pathological response (pCR) - 0% viable tumour cells in the surgical specimen * Near complete pathological response - (near pCR) - \<10% viable tumour * Partial pathological response (pPR) - 10%-50% viable tumour * No pathological response (pNR) - \>50% viable tumour The proportion of participants with a pCR, or near pCR will determine the pathological response rate.

  Week 6

• Feasibility of recruitment

  1. Proportion of patients enrolled in the study from the population of patients presenting to the clinic with new stage II disease, and the reason(s) for exclusion. 2. The proportion of stage II patients with residual disease following diagnostic biopsy. 3. Proportion of eligible patients who consent to the study. 4. The number of patients recruited per month compared to the expected 20 patients over 24 months or 0.84 per month.

  2 years

Secondary Outcomes (12)

• The positive sentinel node biopsy rate at surgery at week 6

  Week 6

• The difference in sentinel lymph node (SLN) mapping between baseline and surgery at week 6.

  Week 6

• The melanoma-related event-free survival (EFS).

  10 years

• Recurrence-free survival

  From surgery to 10 years

• Overall survival

  10 years

Study Arms (1)

Neoadjuvant immunotherapy +/- Adjuvant immunotherapy

EXPERIMENTAL

NEOADJUVANT: All participants will receive neoadjuvant therapy with the fixed dose combination of intravenous relatlimab 160 mg and nivolumab 480 mg x 2 doses on days 1 and 29. SURGERY: All participants will have sentinel lymph node mapping and biopsy prior to a wide local excision of the primary melanoma between days 43 and 56. ADJUVANT: Participants with no pathological response or partial pathological response will receive the fixed dose combination of intravenous relatlimab 160 mg and nivolumab 480 mg for a further 11 doses.

Drug: Relatlimab and nivolumab fixed dose combination (FDC)

Interventions

Relatlimab and nivolumab fixed dose combination (FDC) DRUG

Lymphocyte activation gene-3 (LAG-3) and programmed death-1 (PD-1) are two distinct inhibitory immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes, thus contributing to tumor-mediated T-cell exhaustion. The combination of nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) results in increased T-cell activation compared to the activity of either antibody alone.

Also known as: Opdualag

Neoadjuvant immunotherapy +/- Adjuvant immunotherapy

Eligibility Criteria

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

You may qualify if:

• The patient (or legally acceptable representative, if applicable) provides written informed consent for the trial.
• Male/female patients who are at least 18 years of age on the day of signing informed consent.
• Histologically confirmed primary cutaneous melanoma from a partial core biopsy, punch biopsy, or excisional biopsy with residual macroscopic disease.
• AJCC (8th edition) clinical stage IIB (T3b and T4a) or IIC (T4b) melanoma, or stage IIA (T2b and T3a) melanoma with a ≥ 20% risk of recurrence at 5 years according to the MIA stage II risk calculator (melanomarisk.org.au).
• Synchronous primaries are acceptable if there is certainty that a lesion does not represent in-transit disease and consideration should be given to the need for multiple lymph mapping requirements.
• Past history of a primary melanoma that has been completely excised. If a patient had an SNB, this must be negative.
• Locoregional, nodal or metastatic spread must be ruled out with clinical examination, dermoscopy, RCM and LC-OCT, CT, MRI (or CT) brain, PET, SPECT/CT and lymphoscintigraphy (including ultrasound of draining nodal basin(s)). Patients with demonstrated clinical stage III melanoma are not eligible.
• BRAF / NRAS mutant or wild type melanoma included.
• Availability of the diagnostic tumour sample for translational studies.
• Surgery has been planned for sentinel node biopsy and complete resection of stage II disease. Only cases where a complete surgical resection leading to tumour free margins and which can be safely achieved without being overly morbid is considered "resectable". Resectability of each case has been agreed upon within the context of a Multi-Disciplinary Team (MDT) meeting.
• Eastern Cooperative Oncology Group (ECOG) status 0 to 1.
• Adequate haematological, hepatic, renal and endocrine function on blood pathology testing.
• Anticipated life expectancy of \>12 months.
• Agreement to avoid pregnancy for the duration of treatment: Women of childbearing potential (WOCBP) must not be breastfeeding and must have a negative pregnancy test within 3 days prior to initiation of dosing. She must agree to use an acceptable method of birth control from the time of the negative pregnancy test, through the duration of treatment with the study combination plus 5 half-lives of study treatment for a total of 5 months post-treatment completion.

You may not qualify if:

• Clinical or radiographic evidence of nodal, in-transit, satellite or microsatellite metastases or distant melanoma metastases.
• Any contraindication to the administration of relatlimab or nivolumab.
• A history of allergy or hypersensitivity to study treatment components.
• Prior immunotherapy for any malignancy (including, but not limited to: anti-PD-1, CTLA-4, PDL-1 or anti-LAG3 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways).
• Patients with a condition requiring chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment. The following are permitted:
• Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
• Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if patient is on a stable dose
• Non-absorbed intra-articular steroid injections.
• Has active autoimmune disease that has required systemic treatment in the past 12 months (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). The following are permitted:
• Vitiligo
• Type I diabetes mellitus
• Residual autoimmune hypothyroidism on stable hormone replacement
• Resolved childhood asthma or atopy
• Psoriasis not requiring systemic treatment
• Autoimmune conditions which are not expected to recur in the absence of an external trigger.

Sponsors & Collaborators

• Melanoma Institute Australia: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

Location

MeSH Terms

Conditions

Melanoma

Interventions

relatlimab; Nivolumab; Opdualag

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Georgina Long

  Melanoma Institute Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, single arm clinical trial

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 15, 2022
• Study Start: August 14, 2023
• Primary Completion: December 11, 2025
• Study Completion (Estimated): October 1, 2035
• Last Updated: February 5, 2026

Record last verified: 2026-01

Locations

AU (1)