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Endocrine and neuroendocrine tumours

2491 - Phase I, open-label, dose-escalation study of SNX-5422 plus everolimus in neuroendocrine tumors (NETs)


10 Oct 2016


Endocrine and neuroendocrine tumours


Martin Gutierrez


Annals of Oncology (2016) 27 (6): 136-148. 10.1093/annonc/mdw369


M.E. Gutierrez1, G. Giaccone2, S.V. Liu2, A. Rajan3, U. Guha3, T.R. Halfdanarson4, K.K. Curtis5, P.L. Kunz6, N. Gabrail7, J.M. Hinson8, E.O. Orlemans9

Author affiliations

  • 1 Hematology & Oncology, The John Theurer Cancer Center, 07601 - Hackensack/US
  • 2 Hematology & Oncology, Lombardi Cancer Center Georgetown University, Washington/US
  • 3 Thoracic And Gastrointestinal Oncology, Center for Cancer Research-National Cancer Institute, Bethesda/US
  • 4 Medicine, Mayo Clinic, Rochester/US
  • 5 Internal Medicine, Mayo Clinic, Scottsdale/US
  • 6 Medicine-oncology, Stanford University School of Medicine, Palo Alto/US
  • 7 Hematology, Gabrail Cancer Center, Canton/US
  • 8 Clinical Research, Unicorn Pharma Consulting, Nashville/US
  • 9 Clinical Research, Esanex, Inc., Indianapolis/US


Abstract 2491


SNX-5422 is an orally bioavailable pro-drug of SNX-2112, a highly potent and selective heat shock protein 90 (Hsp90) inhibitor. In preclinical studies, the effects of SNX-2112 and EVR appear at least additive. Previously, at doses of 42-100 mg/m2 of SNX-5422 taken every other day (qod), 2 of 3 patients (pts) with refractory NETs achieved stable disease for >8 cycles. EVR, a mammalian target of rapamycin (mTOR) inhibitor, now has FDA approval for pancreatic NETs and nonfunctional gastrointestinal and pulmonary NETs.


Eligible pts had unresectable gastro-entero-pancreatic or pulmonary NETs and


We enrolled 17 pts (10 male, 7 female; median age 59 years) with NETs. The MTD of SNX-5422 was determined to be 75 mg/m2 in combination with EVR. Dose limiting toxicity was 1 case of G3 diarrhea. Other adverse events in ≥2 pts possibly related to either or both agents included anemia, anorexia, blurred vision (3 pts, all mild, all continued SNX-5422), diarrhea, fatigue, hyponatremia, mucositis, nausea, increased creatinine (EVR), dehydration (EVR), maculopapular rash (EVR), thrombocytopenia (EVR), and weight loss (EVR). All events were G1/G2, except for G3 diarrhea (1 SNX, 1 EVR, 1 both), increased creatinine (1, EVR), hyponatremia (2, EVR). There was also 1 pt who developed possibly related G4 hyponatremia with combination therapy. Six pts with NETs are continuing therapy at this time. Of 14 NET pts evaluable for efficacy, 2 had partial responses (14%; both ongoing, 1 >25 cycles), 8 stable disease (57%), and 4 (29%) progressive disease as best response. Of 8 pts with stable disease, 2 ongoing (1 >23 cycles), 3 study withdrawal (1 personal reasons [minor response], 2 for tolerability) and 3 progressed.


The addition of SNX-5422 75 mg/m2 to EVR in pts with advanced NETs warrants further study.

Clinical trial identification

ClinicalTrials.gov identifier: NCT02063958

Legal entity responsible for the study

Esanex, Inc.


Esanex, Inc.


S.V. Liu: Advisory boards for Genentech/Roche, Boehringer Ingelheim, Ariad, Caris Life Sciences and Biodesix.

P.L. Kunz: Research funding to institution: Advanced Accelerator Applications, Esanex, Genentech, Lexicon, Merck, Oxigene. Advisor/Consultant: Ipsen, Novartis, Lexicon.

J.M. Hinson: Paid consultant to Esanex, Inc.

E.O. Orlemans: Employee and stockholder Esanex, Inx.

All other authors have declared no conflicts of interest.

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