Intralesional Cemiplimab for Patients With Early-Stage Cutaneous Squamous Cell Carcinoma: Results From a Phase 1 Pilot Study Expansion Cohort

Introduction Cemiplimab (cemi), taken intravenously at 350 mg Q3W, is approved by the US FDA for the treatment (tx) of patients (pts) with advanced CSCC not curable by surgery or radiation. However, there is an unmet need for non-surgical tx of pts with early-stage CSCC. This phase 1 pilot trial (NCT03889912) evaluates low-dose intralesional (IL) cemi in early-stage CSCC. The primary objective is to characterize safety and tolerability of IL cemi in pts with early-stage CSCC. Secondary objectives are to describe the objective response rate (including visual complete response [vCR], visual partial response, visual stable disease, and visual progression of disease [vPD]) and pathologic complete response (pCR) rate in index lesions. Methods This is an open-label, sequentially enrolling, phase 1 pilot study with cohort expansions. Dose escalation results have been previously presented. Here, we present data from expansion Cohorts A and B. Key inclusion criteria were: age ≥18 yrs; index lesion ≥1.0–≤2.0 cm (longest diameter); Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1; and adequate hepatic, renal, and bone marrow functions. Key exclusion criteria were immunosuppression and ongoing or recent (within 5 yrs) autoimmune disease requiring systemic immunosuppressant tx. Cohort A received 5 mg IL cemi QW × 6, and Cohort B received 5 mg IL cemi Q2W × 3. Response assessments were performed at Weeks 7 and 13, following modified World Health Organization criteria. Planned surgery was performed at Week 13. Results Twenty-four pts completed the study (12 in each cohort). In Cohort A, the median age was 76.0 yrs and most pts were male (66.7%) with an ECOG PS of 0 (91.7%). Similarly, in Cohort B, the median age was 72.5 yrs and most pts were male (66.7%) with an ECOG PS of 0 (83.3%). Treatment-related adverse events were all grade 1 or 2 and included morbilliform rash and post-inflammatory hyperpigmentation in Cohort A (1 event each) and drug eruption, pruritus, injection-site reaction, and elevated thyroid-stimulating hormone in Cohort B (1 event each). At Week 7, there were 5 vCRs in Cohort A and 2 vCRs in Cohort B. At Week 13, although the numbers of pts with pCRs were similar in both Cohorts (7 in Cohort A, 8 in Cohort B), vPD was only observed in Cohort B (2 pts). Conclusions IL cemi seems effective against early-stage CSCC. Rapid kinetics of response, a lack of disease progression, and a generally acceptable safety profile were observed with the Cohort A regimen (5 mg IL QW × 6). This regimen has been selected for the randomized phase 3 study (NCT06585410). Funding Regeneron Pharmaceuticals, Inc.