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
5773 - A prospective study of diffusion-weighted magnetic resonance imaging for predicting outcome following chemoradiotherapy, in squamous cell carcinomas of the anus.
Presenter: Rebecca Muirhead
Session: Poster Display session 2
Resources:
Abstract
4581 - Timing to achieve complete response (CR) after definitive chemoradiotherapy (ChRT) in patients with squamous cell carcinoma of the anal (SCCAC) with and without HIV infection: a multicenter retrospective study
Presenter: Marcos Camandaroba
Session: Poster Display session 2
Resources:
Abstract
1712 - Planned organ preservation for T2 T3 M0 rectal adenocarcinoma. A possible option using chemoradiotherapy (CRT) and Contact X-ray Brachytherapy (CXB). A French multicenter study.
Presenter: Jean-Pierre Gérard
Session: Poster Display session 2
Resources:
Abstract
4639 - A Phase 1b Study of E7046 (AN0025) in Combination With Radiotherapy/Chemoradiotherapy (RT/CRT) in Preoperative Treatment of Rectal Cancer
Presenter: Lucjan Wyrwicz
Session: Poster Display session 2
Resources:
Abstract
2310 - Upfront radical surgery with total mesorectal excision (TME) versus preoperative chemoradiotherapy followed by TME in clinical stage II/III patients with rectal cancer: a propensity score analysis
Presenter: Ahrong Ham
Session: Poster Display session 2
Resources:
Abstract
2747 - Neoadjuvant chemoradiotherapy with/without lateral lymph node dissection for low rectal cancer: Which patients can benefit?
Presenter: Daisuke Nishizaki
Session: Poster Display session 2
Resources:
Abstract
2877 - The impact of completeness of chemotherapy on the efficacy of irinotecan in the preoperative chemoradiotherapy of locally advanced rectal cancer.
Presenter: Jingwen Wang
Session: Poster Display session 2
Resources:
Abstract
3050 - Feasibility of robot-assisted surgery in elderly patients with rectal cancer
Presenter: Wei-Chih Su
Session: Poster Display session 2
Resources:
Abstract
4109 - Feasibility of chemoradiotherapy in rectal cancer patients with peritumoral abscesses and fistulas: a case-control non-inferiority trial
Presenter: Valerii Ivanov
Session: Poster Display session 2
Resources:
Abstract
4813 - Differential of the nutritional index before and after neoadjuvant chemoradiotherapy as a prognostic factor of recurrence in patients with locally advanced adenocarcinoma of the rectum
Presenter: Leslie Navia-Ortuño
Session: Poster Display session 2
Resources:
Abstract