Nivolumab for locally advanced and metastatic cutaneous squamous cell carcinoma (NIVOSQUACS study)—Phase II data covering impact of concomitant haematological malignancies.

Background: Monoclonal antibodies, such as cemiplimab and pembrolizumab, against the programmed death receptor (PD)‐1 have become the current standard of care and first‐line treatment of advanced cutaneous squamous cell carcinoma (cSCC), proving remarkable clinical benefit and acceptable safety. Objectives: To assess efficacy and safety of the anti‐PD‐1 antibody nivolumab in patients with locally advanced and metastatic cSCC. Methods: Patients received open‐label nivolumab 240 mg intravenously every 2 weeks for up to 24 months. Patients with concomitant haematological malignancies (CHMs), either non‐progressing or stable under active therapy, were eligible for inclusion. Results: Of 31 patients with a median age of 80 years, 22.6% of patients achieved an investigator assessed complete response, resulting in an objective response rate (ORR) of 61.3% and a disease control rate (DCR) of 64.5%. Progression‐free survival (PFS) was 11.1 months, and the median overall survival (OS) was not reached after 24 weeks of therapy. Median follow‐up was 23.82 months. Subgroup analysis of the CHM cohort (n = 11; 35%) revealed an ORR of 45.5%, a DCR of 54.5%, a median PFS of 10.9 months, and median OS of 20.7 months. Treatment related adverse events were reported in 58.1% of all patients (19.4% grade 3, the remaining grade 1 or 2). PD‐L1 expression and CD‐8+ T‐cell infiltration did not significantly correlate with clinical response, although a trend towards a shorter PFS of 5.6 months was observed with PD‐L1 negativity and low CD8+ intratumoral infiltration. Conclusion: This study demonstrated robust clinical efficacy of nivolumab in patients with locally advanced and metastatic cSCCs and a tolerability comparable to data of other anti‐PD‐1 antibodies. Favourable outcomes were obtained despite involving the oldest hitherto reported study cohort for anti‐PD‐1 antibodies and a significant proportion of CHM patients prone to high risk tumours and an aggressive course otherwise typically excluded from clinical trials. [ABSTRACT FROM AUTHOR]