Pilot study to test safety and efficacy of avelumab in small bowel adenocarcinoma (SBA).

Abstract

797 Background: SBA is rare and often grouped with, and treated like, large intestinal adenocarcinomas. However, SBA has a very different microenvironment and could respond differently to the same therapies, potentially lowering efficacy. Also no standard treatments exist due to the lack of prospective randomized trials. We presented data at GI ASCO 2016 that suggested SBAs might benefit from targeting the PD-1/PD-L1 axis based on strong PD-L1 staining in ~50% of SBAs tested. Thus, we designed a pilot phase 2 trial to study safety and efficacy of avelumab in SBA. Methods: Patients (pts) with advanced (not amenable to surgery) or metastatic disease were eligible; ampullary tumors were considered part of the duodenum and allowed. Pts with prior PD-1/PD-L1 were excluded. Avelumab (10 mg/kg) was given every 2 weeks in 14-day cycles, and imaging was performed every 8 weeks. Primary endpoint was response rate (RR). Enrollment of 25 pts were planned, and avelumab would be considered active if ≥4 responses (RR≥16%) were observed (80% power, a = 5%). Secondary endpoints included disease-control rate (DCR) and progression-free survival (PFS). Results: Eight SBA pts (5 small intestine; 3 ampullary) were enrolled, with a majority (88%) being male and a median age of 61 years. Median time on treatment was 3.4 months; 1 patient is still on study with an ongoing partial response (PR). Of 7 efficacy-evaluable patients, 2 had a PR for a RR of 29%; DCR was 71% (5/7). Median PFS was 8.0 months. Most frequent, related adverse events were fatigue (38%), elevated alkaline phosphatase (25%), and infusion related reaction (25%), all ≤G2; a G3 (not serious) hypokalemia and a G4 (serious) diabetic ketoacidosis occurred in 1 pt each. Conclusions: Avelumab was considered safe, and antitumor activity was observed as evidenced by a 29% RR and 71% DCR. Despite this benefit, accrual was slower than expected and the study was closed early due to feasibility. A general clinical observation is that more pts are receiving immunotherapy off-label as the availability of these agents increases. This was a likely contributor to slow accrual, in addition to disease rarity. Analysis of PD-L1 expression, MSI status, and other immune cell markers is planned and will be compared to response. Clinical trial information: NCT03000179 .