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9547 Background: Cemiplimab, a PD-1-axis blocking agent, has recently been approved for unresectable cSCCs. We report results of the CARSKIN study evaluating pembrolizumab in the first-line setting. Methods: Chemotherapy naive patients (pts) with unresectable cSCCs, either locally or regionally advanced or metastatic, and ECOG PS ≤1 were accrued to this multi-institutional phase II trial to assess tumor response rate (RR) and safety of pembrolizumab administered IV (200 mg Q3W) for a period up to 24 months (mo). Baseline PD-L1 expression was centrally assessed on tumor. The primary endpoint was the RR at 15 weeks (wks) per RECIST v1.1 (independent review). A Simon two-stage design was used. Results: From 03/2017 to 01/2018, 39 pts (79% males, median age 79 years) were enrolled. Disease was local (18%), regional (62%) or metastatic (21%); 38% of pts were PS 0. The median number of infusions was 8. The median follow-up was 10.2 mo; 15 pts are still on pembrolizumab. Thirty-four pts were evaluable for tumor response, and 39 for toxicity. The RR at 15 wks was 38.5 % (95% CI: 24–55%) in the ITT population corresponding to 2 CR and 13 PR. The best responses were 3 CR and 12 PR. The DCR was 51% (20/39 including 5 SD) at 15 wks. The median PFS was 8.4 mo and the median OS was not reached. No responder has progressed to date including 2 pts who discontinued pembrolizumab for 6 to 12 mo. Treatment-related AEs (TRAEs) occurred in 67% of pts, including 8% with severe TRAEs (1 gr 3 cholestasis, 1 gr 3 colitis and 1 death due to recurrence of a non-related head and neck cancer) and 10% who discontinued because of a TRAE. Centrally assessed baseline PD-L1 expression was positive in 77% of patients (1% tumor staining threshold), but it failed to predict response at 15 wks with a median PD-L1 expression of 10% in responders and non-responders at 15 wks (P = .55). Conclusions: In this series of 39 elderly pts with unresectable cSCCs, the safety profile was consistent with previous pembrolizumab studies. First-line pembrolizumab provided robust antitumor activity regardless of PD-L1 expression levels. Clinical trial information: NCT02883556.

4140 Background: Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. Methods: BIONADEGE is an ancillary study of the NADEGE cohort that enrolled 347 patients (pts) with SBA from 2009 to 2012. Next generation sequencing investigates the presence of 740 hot spot somatic mutations in 46 genes involved in carcinogenesis. The MSI (MicroSatellite Instable) status was assessed using 5 microsatellites. The MMR (MisMatch Repair) status was assessed by immunochemistry (4 antibodies). Results: A total of 196 tumour samples were collected and 125 pts had conclusive results for mutation analysis. The clinical and tumours characteristics were comparable in the NADEGE and BIONADEGE cohort except for metastatic stage at diagnostic underrepresented in the BIONADEGE cohort (17.7%) due to missing tumour sample. A predisposing disease was reported in 25 (20.0%) cases (among them 14 Lynch syndromes and 7 Crohn diseases). The number of mutation observed was 0 in 9.6% pts, only 1 in 32.0%, 2 in 26.4% and ≥3 in 32.0%. The most frequent genomic alteration were KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%). Altogether, a genomic alteration was observed in 90.3% of tumour. KRAS mutation were more frequent in synchronous metastatic tumour than in localized tumour (72.7% vs 38.2%, p = 0.003). There was no significant difference of mutation rate according to primary location for the most frequently altered gene. With caution to small sample, IDH1 mutation is more frequent and APC mutation never seen in Crohn disease. The rate of dMMR tumor was 38.6% in localized tumour and 0% in synchronous metastatic tumour. After a median follow-up of 55 months (95%CI [44-63]), M0 stage, pN0, pT1-2 were associate with better survival in univariate analysis. No significant prognostic value of genomic alteration was associated with OS. dMMR status was associate with a better prognosis for OS in pts with MMR status determined by immunohistochemistry (HR = 0.55 [0.29-1.01], p = 0.055). Conclusions: A high frequency of targetable alteration is observed in SBA. There is several specificities according to predisposing disease. No association between genomic alteration and prognostic was observed except a trend for a better prognosis associate with dMMR.

9534Background: Patients (pts) with advanced squamous cell carcinoma of the skin (SCCS) have a poor prognosis. Response rate (RR) of 46% with an anti PD-1 (REGN2810) was recently shown in 25 pre-tr...

TPS9596 Background: Treatment options are limited for patients (pts) with locally advanced or metastatic cSCCs. Cisplatin-based combinations have some efficacy but their toxicity often prohibits their use, particularly for the elderly. New therapeutic options are needed. Tumors divert the programmed death receptor 1 (PD-1) pathway suppressing immune control. Pembrolizumab (MK-3475) is a high-affinity humanized monoclonal anti-PD-1 antibody. It leads to dual PD-1 ligand (PD-L1 and PD-L2) blockade that may reactivate the immune surveillance and elicit anti-tumor response. It has antitumor activity in several tumors including head and neck SCCs. Moreover, an efficacy of pembrolizumab in cSCCs has been reported recently in a series of 6 cases. Methods: CARSKIN (ClinicalTrials.gov, NCT02883556) is a French multicenter, open-label, nonrandomized phase 2 trial, designed to evaluate the efficacy and safety of pembrolizumab in 39 pts with unresectable and/or metastatic cSCCs, naive of chemotherapy and of EGFR inhibitors. Pembrolizumab is administered (200 mg IV Q3W) for up to 24 months or until disease progression or unacceptable toxicity. Eligible pts must undergo a baseline biopsy of the tumor prior to treatment for PD-L1 evaluation. Response is to be assessed at baseline, wk 9, 15 and 24, and thereafter Q12W by central radiology review per RECIST 1.1 and per modified RECIST v1.1. The primary objective is response rate (RR) at wk 15 per RECIST 1.1. Secondary efficacy objectives are to assess whether patients with PD-L1+ tumors have a better RR than the whole sample at wk 15 and to assess in the whole sample and in PD-L1+ pts, disease control rate (DCR) at wk15, RR at wk 24, best RR, overall survival (OS), progression free survival (PFS), duration of response / control and time to disease progression. A Simon optimal two-stage design will be used. Four responders among 19 pts will be needed in the 1st step to continue the trial. Overall 9 responses will be needed to conclude the effectiveness. Kaplan-Meier statistics will assess PFS and OS. Adverse events (AEs) will be assessed throughout the study and for 30 d thereafter (6 m for serious AEs) and graded per NCI CTCAE v4.0. Clinical trial information: NCT02883556.