Neoadjuvant Nivolumab and Relatlimab in Cutaneous Squamous Cell Carcinoma

NCT06288191 | Recruiting Phase 2

• 2 other identifiers: MIA2023/490CA224-1065
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to test neoadjuvant therapy with the dual inhibition of Programmed cell death protein 1 (PD-1) and lymphocyte activation gene 3 (LAG-3) immune checkpoint pathways in a cohort of treatment-naïve, resectable stage II to IV cutaneous squamous cell carcinoma on the pathological response rate (pCR) and recurrence-free survival.

Conditions

Cutaneous Squamous Cell Carcinoma

Keywords

neoadjuvant; immunotherapy; pathological response

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate

  Proportion of patients with a pathological complete response, as determined on the week 6 surgical specimen using the guidelines published by the International Neoadjuvant Melanoma Consortium: Complete pathological response (pCR) = 0% viable tumour cells in the surgical specimen

  Week 6

Secondary Outcomes (12)

• Pathological near pathological response (near pCR), partial response (pPR) and pathological non-response (pNR) rate

  Week 6

• Toxicity and tolerability of neoadjuvant immunotherapy and surgery

  Week 24

• Objective response rate to neoadjuvant therapy

  Week 6

• Metabolic response rate to neoadjuvant immunotherapy

  Week 6

• Recurrence-free survival

  10 years

Other Outcomes (4)

• Identification of tissue and blood biomarkers of response / resistance

  1 year

• Profile of the gut microbiome from faecal samples and relationship to response and toxicities.

  Week 6

• The pathological response to RECIST, immune related response criteria and PERCIST response

  Week 6

Study Arms (1)

Neoadjuvant Treatment

EXPERIMENTAL

Nivolumab and relatlimab will be administered in a fixed dose combination (FDC). The dose and dosing regimen for this study is nivolumab 480 mg and relatlimab 160 mg - 2 vials per infusion. All patients are scheduled to receive two doses of nivolumab and relatlimab FDC prior to surgery on days 1 and 29. Patients without a complete pathological response to neoadjuvant therapy may receive standard of care radiotherapy per multidisciplinary team meeting discussion.

Drug: Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination

Interventions

Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination DRUG

Dual inhibition of the distinct LAG3 and PD-1 checkpoint pathways

Also known as: Opdualag

Neoadjuvant Treatment

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age
• Written informed consent
• Histologically confirmed, resectable stage II to IV cutaneous squamous cell carcinoma defined as:
• Non-head and neck cuSCC:
• stage II (T2, N0, M0)
• stage III (T3, N0, M0; or T1-3, N1, M0)
• stage IV (T1-3, N2 or N3, M0; or T4a or T4b, any N, M0)
• Cutaneous head and neck CC:
• stage II (T2, N0, M0)
• stage III (T3, N0, M0)
• stage IV (T4a or T4b, any N, M0)
• In-transit metastases (ITM) are permitted if they are completely resectable. ITM defined as skin or subcutaneous metastases that are \> 20 mm from the primary lesion but not beyond the regional nodal basin.
• Measurable disease according to RECIST version 1.1 criteria (≥10 mm longest diameter for primary lesions and / or ≥10 mm in shortest diameter for lymph nodes as determined by CT imaging) within 2 weeks of the start of study treatment.
• Tumour amenable to a newly obtained core biopsy of a lesion which has not been previously irradiated. Archival tissue from a past primary or nodal cuSCC lesion (if applicable) or tissue taken for current diagnosis will also be collected.
• Previous radiotherapy permitted if performed at a prior site of disease not seen at baseline.

You may not qualify if:

• Clinical or radiographic evidence of distant metastasis
• SCC of the eyelid, vulva, penis and perianus
• Any contraindication to the administration of nivolumab and / or relatlimab
• Prior anti-PD-1, CTLA-4 (Cytotoxic T-lymphocyte associated protein 4), PDL-1 (Programmed death-ligand 1) or LAG 3 (Lymphocyte-Activation Gene 3) antibody exposure, or an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease or any chemotherapy or experimental local or systemic drug treatment
• Active autoimmune disease or a requirement for chronic steroid therapy other than hormone replacement therapy
• The following are permitted:
• Vitiligo
• Type I diabetes mellitus on stable insulin therapy
• 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.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses 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.)

Sponsors & Collaborators

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

Study Sites (1)

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

RECRUITING

MeSH Terms

Interventions

Nivolumab; relatlimab; Opdualag

Intervention Hierarchy (Ancestors)

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

Study Officials

• Ines Da Silva

  Melanoma Instiute Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Osorio

CONTACT

+61 2 9911 7296; monica.osorio@melanoma.org.au

Maria Gonzalez

CONTACT

+61 2 9911 7200; maria.gonzalez@melanoma.org.au

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, single centre, clinical trial

Study Record Dates

• First Submitted: February 4, 2024
• First Posted: March 1, 2024
• Study Start: June 21, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): July 1, 2036
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)