A dose escalation/expansion study evaluating dose, safety, and efficacy of the novel tyrosine kinase inhibitor surufatinib, which inhibits VEGFR 1, 2, & 3, FGFR 1, and CSF1R, in US patients with neuroendocrine tumors

Arvind Dasari, Erika P. Hamilton, Gerald S. Falchook, Judy S. Wang, Daneng Li, Max W. Sung, Caly Chien, Shivani Nanda, Christopher Tucci, Marjo Hahka-Kemppinen, Andrew Scott Paulson

Research output: Contribution to journalArticlepeer-review

Abstract

Surufatinib, is a potent inhibitor of vascular endothelial growth factor receptors 1–3; fibroblast growth factor receptor-1; colony-stimulating factor 1 receptor. This Phase 1/1b escalation/expansion study in US patients with solid tumors evaluated 5 once daily (QD) surufatinib doses (3 + 3 design) to identify maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and evaluate safety and efficacy at the RP2D in 4 disease-specific expansion cohorts including pancreatic neuroendocrine tumors [pNET] and extrapancreatic NETs [epNET]. MTD and RP2D were 300 mg QD (escalation [n = 35]); 5 patients (15.6%) (Dose Limiting Toxicity [DLT] Evaluable Set [n = 32]) had DLTs. Pharmacokinetics were dose proportional. Estimated progression-free survival (PFS) rates at 11 months were 57.4% (95% confidence interval [CI]: 28.7, 78.2) and 51.1% (95% CI: 12.8, 80.3) for pNET and epNET expansion cohorts, respectively. Median PFS was 15.2 (95% CI: 5.2, not evaluable) and 11.5 (95% CI: 6.5,11.5) months. Response rates were 18.8% and 6.3%. The most frequent treatment-emergent adverse events (both cohorts) were fatigue (46.9%), hypertension (43.8%), proteinuria (37.5%), diarrhea (34.4%). Pharmacokinetics, safety, and antitumor efficacy of 300 mg QD oral surufatinib in US patients with pNETs and epNETs are consistent with previously reported studies in China and may support applicability of earlier surufatinib studies in US patients. Clinical trial registration: Clinicaltrials.gov NCT02549937.

Original languageEnglish
Pages (from-to)421-430
Number of pages10
JournalInvestigational New Drugs
Volume41
Issue number3
DOIs
StatePublished - Jun 2023

Keywords

  • Extrapancreatic neuroendocrine tumors
  • Pancreatic neuroendocrine tumors
  • Surufatinib
  • Vascular endothelial growth factor receptor

Fingerprint

Dive into the research topics of 'A dose escalation/expansion study evaluating dose, safety, and efficacy of the novel tyrosine kinase inhibitor surufatinib, which inhibits VEGFR 1, 2, & 3, FGFR 1, and CSF1R, in US patients with neuroendocrine tumors'. Together they form a unique fingerprint.

Cite this