1393PSafety and tolerability of surufatinib in western patients with solid tumours

Abstract Background Surufatinib, also called sulfatinib, is a targeted inhibitor of the tyrosine kinases VEGFR1, 2, and 3, FGFR1, and CSF1R. The safety profile of surufatinib was favorable in 2 completed studies (NCT 02133157 and 02267967) conducted in Chinese cancer patients (pts). Surufatinib has demonstrated anti-tumor activity in pts with advanced, well-differentiated neuroendocrine tumors (NETs) (response rate 17%) and is being evaluated in phase III trials. Methods This is an ongoing dose escalation (ESC)/dose expansion (EXP) study being conducted in the United States to establish safety in Western pts. The ESC phase enrolled pts with any solid tumor. The EXP phase is enrolling pts with biliary tract cancers, pancreatic NETs, or extrapancreatic NETs. The primary objective is to evaluate safety and tolerability and to determine the maximum-tolerated dose (MTD)/recommended phase II dose (RP2D). Results As of the data cut-off date of 11 Feb 2019, 57 pts who enrolled and received ≥ 1 dose of surufatinib (35 in ESC, 22 in EXP), 23 were male, and median age was 62 years. The most common primary malignancies were bile duct (n=17), pancreatic NET (n=16), endometrial (n=3), and ovary (n=3). There were 6 pts in ESC with a DLT; 1/6 in the 100mg QD (fatigue), 1/11 in the 300mg QD (hypertension), and 4/13 in the 400mg QD (2 proteinuria, 1 thrombocytopenia, and 1 ALT elevation) cohorts. The MTD/RP2D was 300mg QD. The most frequent (≥20% incidence) treatment emergent adverse events (AEs) were diarrhea (35%), nausea (33%), fatigue (26%), hypertension (26%), and vomiting (21%). Grade ≥ 3 AEs were reported in 56% of pts; the most frequent (≥ 5% incidence) were hypertension (12%), diarrhea (5%), fatigue (5%), and proteinuria (5%). Fifteen pts had serious adverse events. Preliminary pharmacokinetic data (n=9) showed dose proportional increase in exposure and slightly higher (30%) exposure (AUC) compared to the Chinese pt population. Partial response was seen in 4 pts, with (by primary site, dose)1 endometrial, 100mg QD; 1 bile duct, 300mg QD; and 2 pancreatic NET, 300mg QD. Conclusions The safety profile of surufatinib at the RP2D in these Western cancer pts is consistent with those from completed studies performed in Chinese pts and consistent with VEGF targeted therapy. Preliminary data show promising efficacy. Clinical trial identification NCT02549937. Editorial acknowledgement Hoang-Lan Nguyen, PhD, Hutchison MediPharma (US), Inc. Legal entity responsible for the study Hutchison MediPharma, Limited. Funding Hutchison MediPharma, Limited. Disclosure E. Hamilton: Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy: Flatiron Health; Advisory / Consultancy, Research grant / Funding (institution): Cascadian Therapeutics; Research grant / Funding (institution): Hutchison Medipharma; Research grant / Funding (institution): Oncomed; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): StemCentrx; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Curis; Research grant / Funding (institution): Verastem; Research grant / Funding (institution): Zymeworks; Research grant / Funding (institution): Syndax; Research grant / Funding (institution): Lycera; Research grant / Funding (institution): Rgenix; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): TapImmune; Research grant / Funding (institution): BerGenBio; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Kadmon; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): H3 Biomedicine; Research grant / Funding (institution): Radius Health; Research grant / Funding (institution): Acerta; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): FujiFilm; Research grant / Funding (institution): eFFECTOR. J.S. Wang: Speaker Bureau / Expert testimony: AstraZeneca. D. Li: Advisory / Consultancy, Speaker Bureau / Expert testimony: Lexicon; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Exelixis; Advisory / Consultancy: Bayer; Speaker Bureau / Expert testimony: Advanced Accelerator Applications; Research grant / Funding (institution): Brooklyn ImmunoTherapeutics. N.A. Dasari: Advisory / Consultancy: Lexicon; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Crinetics; Research grant / Funding (self): Merck; Research grant / Funding (self): Hutchison MediPharma; Research grant / Funding (self): eFFECTOR; Research grant / Funding (self): Eisai. S. Paulson: Advisory / Consultancy: AAA; Advisory / Consultancy, Research grant / Funding (institution): Taiho; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Eisai; Advisory / Consultancy: Amgen; Shareholder / Stockholder / Stock options: Aptose; Shareholder / Stockholder / Stock options: Seattle Genetics; Shareholder / Stockholder / Stock options: Immunomedics; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Exelixis. A.L. Cohn: Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Bristol-Myers Squibb. N.P. Sauter: Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. M. Kania: Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. J. Kauh: Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. G.S. Falchook: Licensing / Royalties: Wolters Kluwer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Fujifilm; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Research grant / Funding (institution), Travel / Accommodation / Expenses: Millenium; Speaker Bureau / Expert testimony: Total Health Conferencing; Research grant / Funding (institution): 3-V Biosciends; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): ADC Therapeutics; Research grant / Funding (institution): Aileron; Research grant / Funding (institution): ASCO; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): ARMO; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Beigene; Research grant / Funding (institution): Bioatla; Research grant / Funding (institution): Biothera; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Ciclomed; Research grant / Funding (institution): Curegenix; Research grant / Funding (institution): Curis DelMar; Research grant / Funding (institution): eFFECTOR; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Genmab; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Hutchison MediPharma Ltd; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Jacobio; Research grant / Funding (institution): Jounce; Research grant / Funding (institution): Koltan; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Merck; Research grant / Funding (institution): miRNA Therapeutics; Research grant / Funding (institution): Nationals Institutes of Health; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Oncomed; Research grant / Funding (institution): Oncothyreon; Research grant / Funding (institution): Precision Oncology; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Rgenix; Research grant / Funding (institution): Strategia; Research grant / Funding (institution): Syndax; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Tarveda; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Tocagen; Research grant / Funding (institution): MD Anderson Cancer Center; Research grant / Funding (institution): Vegenics.