Work

Integrated tumor and circulating immune profiling in the NEO-CESQ trial of perioperative cemiplimab for resectable cutaneous squamous cell carcinoma

Year: 2026

Type: article

Abstract: Background Perioperative immune checkpoint inhibition is emerging as a promising strategy for high-risk, resectable cutaneous squamous cell carcinoma (CSCC). However, biomarkers capable of predicting pathological response and recurrence remain undefined. We report clinical and translational findings from NEO-CESQ ( NCT04632433), a multicenter, single-arm phase II trial evaluating neoadjuvant plus adjuvant cemiplimab in patients with stage III–IV resectable CSCC.Methods Patients received neoadjuvant cemiplimab followed by surgery and adjuvant treatment. The primary endpoint was major pathological response (MPR; <10% viable tumor) assessed in the intention-to-treat population. Survival outcomes were estimated using HRs with 95% CIs. Exploratory translational analyses included baseline tumor transcriptomics (NanoString PanCancer IO 360) and longitudinal serum cytokine profiling. Differential expression and signature enrichment analyses were performed to identify molecular correlates of response. An exploratory transcriptional classifier associated with recurrence-free survival was developed, and its performance was evaluated using the area under the curve (AUC).Results MPR was achieved in 11 of 25 patients (44%), while pathological complete response (pCR) occurred in nine patients (36%). With a median follow-up of 42 months, MPR was associated with improved event-free survival (HR 0.16, 95% CI 0.03–0.75), although recurrence events were limited. Patients achieving pCR exhibited lower circulating interleukin 6 (IL-6) levels prior to adjuvant therapy compared with non-pCR patients, but IL-6 did not significantly discriminate MPR status or survival outcomes. Tumor transcriptomic analyses revealed enrichment of interferon-γ-related signatures in responders, whereas non-responders showed higher expression of WNT5A and CD276. An exploratory 10-gene classifier (“NeoSquamos”) demonstrated an AUC of 0.838 for recurrence-free survival prediction, though based on a limited number of events.Conclusions These findings provide an integrated view of tumor and systemic immune dynamics during perioperative programmed death 1 blockade in CSCC. Candidate biomarkers, including transcriptomic signatures and circulating cytokines, may help refine risk stratification, although prospective validation in larger cohorts is required.Trial registration number NCT04632433.

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-016059