ctDNA Analysis Shows Cemiplimab Benefit Across MRD Subgroups in CSCC

In an interview at the 2026 ESMO Congress, Danny Rischin, director of medical oncology at Peter MacCallum Cancer Centre in Melbourne, Australia, discussed findings from an exploratory circulating tumor DNA (ctDNA) analysis of the phase 3 C-POST trial (NCT03969004), which evaluated adjuvant cemiplimab (Libtayo) vs placebo in patients with high-risk cutaneous squamous cell carcinoma (CSCC) following surgery and radiotherapy.

A protocol amendment allowed investigators to collect blood samples for ctDNA analysis using a tumor-informed, ultrasensitive next-generation sequencing assay. Of 415 patients enrolled in the trial, 286 were eligible for ctDNA collection, and evaluable results were available for 191 patients. Rischin emphasizes that patients had no evidence of disease on imaging before the baseline blood samples were collected, allowing investigators to assess whether ctDNA could detect molecular residual disease (MRD) not visible on scans.

MRD positivity rates were similar between the cemiplimab and placebo groups, at approximately 18% and 19%, respectively. The analysis showed that MRD status was prognostic, with significantly different outcomes between MRD-positive and MRD-negative patients. Patients with detectable MRD who received placebo had particularly poor outcomes.

Cemiplimab was associated with improved disease-free survival (DFS) in both MRD subgroups. The HR for DFS was 0.45 among MRD-negative patients and 0.24 among MRD-positive patients, suggesting a potentially greater relative benefit among patients with detectable ctDNA.

Rischin highlights the potential of ctDNA testing to identify patients at increased risk of recurrence despite having no detectable disease on imaging. The findings also indicate that patients with MRD-positive results may benefit from adjuvant cemiplimab.