Abstract 2191
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 100 mg QD (fatigue), 1/11 in the 300 mg QD (hypertension), and 4/13 in the 400 mg QD (2 proteinuria, 1 thrombocytopenia, and 1 ALT elevation) cohorts. The MTD/RP2D was 300 mg 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, 100 mg QD; 1 bile duct, 300 mg QD; and 2 pancreatic NET, 300 mg 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.
Resources from the same session
3905 - Loss of CDX-2 expression is an independent poor prognostic biomarker in colorectal cancer
Presenter: Krittiya Korphaisarn
Session: Poster Display session 2
Resources:
Abstract
3963 - Robot-assisted natural orifice specimen extraction surgery for radical resection of colorectal cancer
Presenter: Zhengchuan Niu
Session: Poster Display session 2
Resources:
Abstract
3989 - Bevacizumab as adjuvant treatment for colon cancer: Updated results from the AVANT phase III Study by the GERCOR Group
Presenter: Thierry André
Session: Poster Display session 2
Resources:
Abstract
4741 - Real world data on adjuvant chemotherapy for high-risk stage II colorectal cancer – the role of tumor side
Presenter: Camila Araujo de Carvalho
Session: Poster Display session 2
Resources:
Abstract
4973 - Oncological Outcome and Safety of Bevacizumab (BV) Therapy in Patients with Occlusive Colon Cancer and Self-Expandable Metal Stents (SEMS)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 2
Resources:
Abstract
2295 - Active chronic hepatitis B increases the risk of liver metastasis of colorectal cancer- a retrospective clinical study of 7187 consecutive cases of newly diagnosed colorectal cancer
Presenter: Lei Zhao
Session: Poster Display session 2
Resources:
Abstract
3845 - Comprehensive Evaluation of Recurrence Risk (CERR) Score for Colorectal Liver Metastases: Development and Validation
Presenter: Wei Ye
Session: Poster Display session 2
Resources:
Abstract
1976 - BRAF-mutated colorectal metastases: what is the benefit of liver surgery? Results from a cohort of 91 patients.
Presenter: Sahir Javed
Session: Poster Display session 2
Resources:
Abstract
2688 - The smallest colorectal liver metastasis size as a prognosis factor after laparoscopic liver resection
Presenter: Baptiste Cervantes
Session: Poster Display session 2
Resources:
Abstract
4961 - Validation of GAME score risk groups in resected colorectal cancer liver metastases and the prognostic relevance of KRAS, NRAS and BRAF mutation analysis
Presenter: Berta Martin-Cullell
Session: Poster Display session 2
Resources:
Abstract