LAUSR

e21020 Background: Patients (pts) with unresectable/metastatic CSCC have a poor prognosis, and until recently had limited treatment options. Based on encouraging efficacy in case report series, we conducted a phase 2 trial to evaluate the efficacy of CAP or 5-FU in combination with Peg-IFNA-2b in advanced CSCC. Methods: Eligible pts with measurable unresectable/metastatic CSCC were treated with CAP (1000mg/m2 PO twice daily days 1-14) or 5-FU (800 mg/m2 IV days 1-4), and Peg-IFNA-2b (subcutaneously at 3ug/kg weekly) in a 21-day cycle for up to 9 cycles, intolerable toxicity or progression. The primary objective was to assess overall response rate (ORR) while secondary objectives were safety and survival. Exploratory correlative tissue immune markers were studied using multiplex immunohistochemistry (mIHC) on pre- and post-treatment optional tumor biopsies. Results: Poor accrual led to early study closure after enrolling 8 pts. All pts were male, median age was 73.5 yrs. The ORR was 25% (1 CR, 1 PR); 4 pts had SD, 1 with PD and 1 withdrew consent prior to first restaging. The pt with CR had previously progressed on anti-PD1 therapy; tissue mIHC from this pt showed an increase in CD8+ cells prior to starting trial therapy. Due to the low sample size the 6 and 12-month survival estimates for OS and PFS are the same, 87.5% and 50% for 6 and 12 months respectively. Grade ≥ 3 or higher toxicities included decreased WBC (n = 3), fatigue, failure to thrive, anemia (all n = 2), and neutropenia, dehydration, hand-foot syndrome (all n = 1). Dose reductions were frequently encountered. Conclusions: Combination CAP/5-FU plus Peg-IFNA-2b has activity in advanced CSCC but with considerable toxicity at studied doses. The small sample size precludes meaningful conclusions on efficacy, though the CR observed post-PD1 progression might warrant further investigation of this combination as a therapeutic strategy given the recent approval of cemiplimab in CSCC. Clinical trial information: NCT02218164.