Activity & Safety of Spartalizumab (PDR001) in Patients (pts) With Advanced Neuroendocrine Tumors (NET) of Pancreatic (Pan), Gastrointestinal (GI),...

Date 22 October 2018
Event ESMO 2018 Congress
Session Proffered paper session - NETs and endocrine tumours
Topics Neuroendocrine Tumours
Clinical Research
Presenter James Yao
Citation Annals of Oncology (2018) 29 (suppl_8): viii467-viii478. 10.1093/annonc/mdy293
Authors J.C. Yao1, J. Strosberg2, N. Fazio3, M.E. Pavel4, P. Ruszniewski5, E. Bergsland6, D. Li7, S. Tafuto8, N. Raj9, D. Campana10, S. Hijioka11, M. Raderer12, R. Guimbaud13, P. Gajate14, S. Pusceddu15, A. Reising16, E. Degtyarev17, B. Mookerjee18, P. Aimone19, S. Singh20
  • 1Department Of Gastrointestinal Medical Oncology, University of Texas/MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 2Department Of Medicine, Moffitt Cancer Center, Tampa, 33612 - Florida/US
  • 3Unit Of Gastrointestinal Medical Oncology And Neuroendocrine Tumors, European Institute of Oncology, 20141 - Milan/IT
  • 4Department Of Endocrinology, University of Erlangen-Nuremberg, 91054 - Erlangen/DE
  • 5Gastroenterology And Pancreatology Department, Beaujon Hospital, 92110 - Clichy/FR
  • 6Division Of Hematology/oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco/US
  • 7Department Of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center and Beckman Research Institute, 91009-91010 - Duarte/US
  • 8Dipartimento Di Oncologia Addominale, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, ENETS Center of Excellence, 80131 - Naples/IT
  • 9Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, 10065 - New York/US
  • 10Department Of Medical And Surgical Sciences, Policlinico Sant'Orsola-Malpighi, 40138 - Bologna/IT
  • 11Department Of Gastroenterology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 12Clinical Division Of Oncology, Medical University of Vienna, 1090 - Vienna/AT
  • 13Department Of Digestive Medical Oncology, CHU de Toulouse, Toulouse/FR
  • 14Clinical Oncology Department, Hospital Universitário Ramón y Cajal, 28001 - Madrid/ES
  • 15Department Of Medical Oncology, Fondazione IRCCS Istituto Naz, 20133 - Milan/IT
  • 16Opm Translational Precision Oncology, Novartis Pharmaceuticals Corporation, East Hanover, 07936 - New Jersey/US
  • 17Oncology Biostatistics, Novartis Pharma AG, Basel/CH
  • 18Global Drug Development, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 19Global Drug Development, Novartis Pharma AG, 4056 - Basel/CH
  • 20Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto/CA



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.


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.


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: 1308O

Partial response, %
Stable disease, %53.354.559.455.814.3
Unknown, %
Disease control rate, %73.357.659.463.219.0

All responses were observed in atypical carcinoid cohort.


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


Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.


Novartis Pharmaceuticals Corporation.

Editorial Acknowledgement


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.