Neoadjuvant Nivolumab and Relatlimab in Cutaneous Squamous Cell Carcinoma

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

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

Proportion of patients with each non-pCR response category, as determined on the week 6 surgical specimen using the guidelines published by the International Neoadjuvant Melanoma Consortium (INMC): * Major pathological response (pCR + near-pCR), * Near complete pathological response - (near pCR) - \>0% - ≤10% viable tumour * Partial pathological response (pPR) - \>10 - ≤50% viable tumour * Non pathological response (pNR) - \>50% viable tumour

Toxicity and tolerability of neoadjuvant immunotherapy and surgery

The proportion of patients with adverse events (AE) per Common Terminology Criteria for Adverse Events (CTCAE), from initiation of study treatment until at least 135 days after the end of treatment. Outcome measures include the proportion of patients with each of the following measures: 1. An AE by CTCAE term / grade 2. AEs attributable to neoadjuvant treatment 3. Grade 3/4/5 AEs by AE term 4. The duration of events reported in (a) 5. Delayed study treatment and/or delay surgery due to an AE 6. A requirement to discontinue study treatment early due to an AE 7. Oral or parenteral steroid treatment for immune-related adverse events. 8. Post-operative complications (e.g. seroma formation, wound infection or lymphoedema) and duration of events. 9. Post-operative complications at 3, 12 and 48 weeks using the Clavien-Dindo Classification. 10. Surgeon's assessment of 'operability' and morbidity from baseline and at surgery per INMC questionnaires.

Objective response rate to neoadjuvant therapy

The proportion of patients within each response category, as assessed using RECIST version 1.1, comparing week 6 to baseline CT and MRI. Objective response rate= CR and PR

Metabolic response rate to neoadjuvant immunotherapy

The proportion of patients within each response category, as assessed using the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) and the standardised uptake value (SUV) comparing week 6 to baseline positron emission tomography (PET) scan. Metabolic response rate = Complete metabolic response (CMR) and partial metabolic response (PMR).

Identification of tissue and blood biomarkers of response / resistance

Identification of biomarkers in tumour tissue and blood that may be predicitve of the response or resistance to neoadjuvant immunotherapy.

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

Identification of the type and abundance of gut microbes and the correlation with treatment response and incidence of treatment-related toxicities.

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

Proportion of patients with concordance across all tumour evaluations

Assessment of the response to neoadjuvant using the immune-related response criteria (irRC) and correlate the assessment with the RECIST 1.1 response at each timepoint

Bi-dimensional measurements of all target lesions per irRC guidelines