Activity & safety of spartalizumab (PDR001) in patients (pts) with advanced neuroendocrine tumors (NET) of pancreatic (Pan), gastrointestinal (GI), or thoracic (T) origin, & gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who have progressed on prior treatment (Tx) (2018)

Background: PDR001 is a high-affinity, humanized, anti-PD-1 IgG4 antibody that blocks PD-L1 & PD-L2 binding to PD-1. A phase 2, multi-center study assessed the efficacy & safety of PDR001 in pts with nonfunctional well- & poorly-differentiated (diff) neuroendocrine neoplasms. Methods: Pts with advanced NET (GI, Pan, or T origin) who have progressed on prior Tx (including everolimus), & GEP NEC pts who have progressed on 1 line of chemoTx, were enrolled, regardless of PD-L1 expression. Primary endpoint was overall response rate (central; ORR). Secondary endpoints were duration of response, biomarker analyses & safety. Results: Total 116 pts enrolled (33 panNET, 32 GI NET, 30 T NET, & 21 GEP NEC). Pts received PDR001 (400 mg, q4w) via 30 min IV infusion until disease progression/unacceptable toxicity. At data snapshot cut-off (Feb 09, 2018) with median follow-up of 7.6 mo in NET and 6 mo in GEP NEC, ORR was 7.4% in well-diff NET (pooled) & 4.8% in poorly-diff GEP NEC. Pts with T NET had higher ORR, while, clinical activity was marginal in other cohorts (Table). Most common grade 3/4 adverse events (>2.5%) regardless of causality were abdominal & back pain, anemia, dyspnea, & hypertension. PD-L1 expression was generally low; GEP NEC pts had a higher proportion of PD-L1 expression in immune cells >1% (43% vs T NET: 19%; panNET: 23%; GI NET: 10%). Biomarker results suggest a potential link between TIM-3 expression & lack of Tx response. Additional biomarker data will be presented.Table: 1308OT*All responses were observed in atypical carcinoid cohort.PGIOverall NET (T+P+GI)GEP NECPartial response, %20.03.007.44.8Stable disease, %53.354.559.455.814.3Unknown, %10.03.06.36.314.3Disease control rate, %73.357.659.463.219.0* All responses were observed in atypical carcinoid cohort. Open table in a new tab Conclusions: These preliminary results suggest clinical activity of spartalizumab in pts with well-diff nonfunctional NET of T origin. Further studies are needed to explore the role of immunotherapy combinations, identifying predictive biomarkers for immunoncology (IO) response or strategies to increase response to IO in this pt population. Clinical trial identification: NCT02955069. Legal entity responsible for the study: Novartis Pharmaceuticals Corporation. Funding: Novartis Pharmaceuticals Corporation. Disclosure: J.C. Yao: Grants: Novartis, during the conduct of the study; Personal fees: Novartis; Personal fees: Ipsen, outside the submitted work. J. Strosberg: Personal fees: Novartis, Ipsen, Lexicon, outside the submitted work. N. Fazio: Consultation fees: Novartis, Ipsen, Pfizer, AAA, Merck Serono. M.E. Pavel: Personal fees: Novartis, Ipsen, Pfizer, Lexicon, during the conduct of the study. P. Ruszniewski: Personal fees: Ipsen, Novartis, AAA, outside the submitted work. E. Bergsland: Other: Novartis and Merck, during the conduct of the study. D. Li: Personal fees: Novartis, Ipsen, Lexicon, Exelixis, outside the submitted work. M. Raderer: Travel, accommodations, meeting expenses: Roche, Novartis, Ipsen, Jansse Cilag, Amgen. S. Pusceddu: Travel grant, Honoraria, Personal fees: Novartis, Ipsen, Italfarmaco, Pfizer, AAA. A. Reising, P. Aimone: Employee: Novartis. E. Degtyarev: Employee, Personal fee: Novartis, during the conduct of the study. B. Mookerjee: Employee, Stock options: Novartis S. Singh: Honoraria, Travel funding: Ipsen, Pfizer, Novartis; Research funding: EMD Serono, Novartis. All other authors have declared no conflicts of interest.