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
5185 - Systemic administration of the hyaluronidase-expressing oncolytic adenovirus VCN-01 in patients with advanced or metastatic pancreatic cancer: first-in-human clinical trial
Presenter: Rocio Garcia-Carbonero
Session: Poster Display session 2
Resources:
Abstract
4842 - The analysis of genomic signatures of head and body/tail of pancreatic cancer in Chinese patients
Presenter: Qi Ling
Session: Poster Display session 2
Resources:
Abstract
4988 - MGMT methylation in metastatic pancreatic cancer (mPAC): a single center experience
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5035 - Advantage of three-dimensional image analysis of pancreatic cancer using computed tomography
Presenter: Seung Bae Yoon
Session: Poster Display session 2
Resources:
Abstract
1465 - Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) with S-1 in patients with stage IV pancreatic cancer.
Presenter: Susumu Hijioka
Session: Poster Display session 2
Resources:
Abstract
1982 - Impact of anatomic site of biliary tract tumour origin and conditional probability of survival (CS): results from 15 prospective advanced first-line clinical trial
Presenter: Mairead McNamara
Session: Poster Display session 2
Resources:
Abstract
2244 - FOLFOXIRI versus FOLFIRINOX in first-line chemotherapy in patients with advanced pancreatic cancer: a propensity score analysis
Presenter: Angélique Vienot
Session: Poster Display session 2
Resources:
Abstract
4557 - Cellfree tumor-DNA (cfDNA) as a very early predictor of therapeutic outcome in pancreatic ductal adenocarcinoma (PDAC)
Presenter: Sabine Payr
Session: Poster Display session 2
Resources:
Abstract
4406 - Comprehensive genomic profiling (CGP) of gall bladder adenocarcinoma (GBAC) in patients from distinct ancestral populations
Presenter: Milind Javle
Session: Poster Display session 2
Resources:
Abstract
4283 - Phase II Monotherapy Efficacy of Cancer Metabolism Targeting SM-88 in Heavily Pre-Treated PDAC Patients.
Presenter: Allyson Ocean
Session: Poster Display session 2
Resources:
Abstract