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This Phase 1\/1b escalation\/expansion study in US patients with solid tumors evaluated 5 once daily (QD) surufatinib doses (3\u2009+\u20093 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\u00a0mg QD (escalation [n\u2009=\u200935]); 5 patients (15.6%) (Dose Limiting Toxicity [DLT] Evaluable Set [n\u2009=\u200932]) 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\u00a0mg 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. <jats:bold>Clinical trial registration<\/jats:bold>: Clinicaltrials.gov NCT02549937.<\/jats:p>","DOI":"10.1007\/s10637-023-01359-2","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T11:02:16Z","timestamp":1681902136000},"page":"421-430","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A dose escalation\/expansion study evaluating dose, safety, and efficacy of the novel tyrosine kinase inhibitor surufatinib, which inhibits VEGFR 1, 2, &amp; 3, FGFR 1, and CSF1R, in US patients with neuroendocrine tumors"],"prefix":"10.1007","volume":"41","author":[{"given":"Arvind","family":"Dasari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika P.","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald S.","family":"Falchook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy S.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daneng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max W.","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caly","family":"Chien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Nanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Tucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo","family":"Hahka-Kemppinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Scott","family":"Paulson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"1359_CR1","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.annonc.2020.03.304","volume":"31","author":"M Pavel","year":"2020","unstructured":"Pavel M, \u00d6berg K, Falconi M, Krenning EP, Sundin A, Perren A et al (2020) Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. 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This study was conducted in full accordance with the International Council for Harmonization Good Clinical Practice Tripartite Guideline (E6) and any applicable national and local laws and regulations. A personally signed and dated informed consent form was obtained from each patient (if the patient was able) before any study-specific procedures or assessments were done and after the aims, methods, anticipated benefits, and potential hazards were explained, according to national and local IRB requirements.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"CC, SN, CT, and MH-K are employees of HUTCHMED International Corporation and may own HUTCHMED International Corporation stock and\/or stock options.AD reports grants or contracts from HUTCHMED International Corporation, Eisai and Crinetics; consulting fees from HUTCHMED, Crinetics, and AAA; and Advisory Board participation for Oncobay.EPH reports payment to the institution for research funding as PI for studies from HUTCHMED International Corporation, Abbvie, Acerta Pharma, Accutar Biotechnology, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, Black Diamond, Bliss BioPharmaceuticals, Boehringer Ingelheim, Cascadian Therapeutics, Clovis, Compugen, Cullen-Florentine, Curis, CytomX, Daiichi Sankyo, Dana Farber Cancer Inst, Dantari, Deciphera, Duality Biologics, eFFECTOR Therapeutics, Ellipses Pharma, Elucida Oncology, EMD Serono, Fochon, FujiFilm, G1 Therapeutics, H3 Biomedicine, Harpoon, Zymeworks, Immunogen, Immunomedics, Incyte, Infinity Pharmaceuticals, Investis Bio, Jacobio, Karyopharm, Leap Therapeutics, Lilly, Lycera, Mabspace Biosciences, Macrogenics, MedImmune, Merck, Mersana, Merus, Millennium, Molecular Templates, Myraid Genetic Laboratories, Novartis, Nucana, Olema, OncoMed, Onconova Therapeutics, ORIC Pharmaceuticals, Orinove, Pfizer, PharmaMar, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Plexxikon, Radius Health, Regeneron, Relay Therapeutics, Repertoire Immune Medicine, Rgenix, Roche\/Genentech, SeaGen, Sermonix Pharmaceuticals, Shattuck Labs, Silverback, StemCentRx, Sutro, Syndax, Syros, Taiho, TapImmune, Tesaro, Tolmar, Torque Therapeutics, Treadwell Therapeutics, Verastem, Vincerx Pharma, Zenith Epigenetics; payment to the institution for consulting work from Arcus, Arvinas, AstraZeneca, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, Greenwich LifeSciences, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Orum Therapeutics, Pfizer, Propella Therapeutics, Puma Biotechnology, Relay Therapeutics, Roche\/Genentech, SeaGen, Silverback Therapeutics.GSF reports Royalties (self): Wolters Kluwer (2014-present); Advisory role (to institution): AbbVie (2022), Fujifilm (2018), Silicon (2020, 2021), Navire (2021), Turning Point (2021), Predicine (2021), Inspirna (2021), Regeneron (2021), Jubilant (2022), BostonGene (2022), Teon (2022), Merck (2022); Advisory role (self): EMD Serono (2010, 2011); Speakers honorarium for CME: Total Health Conferencing (2019), Rocky Mountain Oncology Society (2020); Travel (self, for work and\/or research related to institution): Amgen (2022), Bristol-Myers Squibb (2015), EMD Serono (2011, 2012, 2013), Fujifilm (2018), Millennium (2013), Sarah Cannon Research Institute (employer, at least once yearly), Synthorx\/Sanofi (2022); Research funding [to institution, for any trial for which I have been the PI (ever) or subinvestigator (minimum last 4 years)]: 3-V Biosciences, Abbisko, Abbvie, ABL Bio, ADC Therapeutics, Accutar, Agenus, Aileron, American Society of Clinical Oncology, Amgen, ARMO\/Eli Lilly, Artios, AstraZeneca, Bayer, BeiGene, Bioatla, Bioinvent, Biothera, Bicycle, Black Diamond, Boehringer Ingelheim, Celgene, Celldex, Ciclomed, Curegenix, Curis, Cyteir, Daiichi, DelMar, eFFECTOR, Eli Lilly, EMD Serono, Epizyme, Erasca, Exelixis, Freenome, Fujifilm, Genmab, GlaxoSmithKline, Hutchison MediPharma, IGM Biosciences, Ignyta, Immunitas, ImmunoGen\/MacroGenics, Incyte, Jacobio, Jazz, Jounce, Jubilant, Kolltan, Loxo\/Bayer, MedImmune, Merck, Metabomed, Millennium, Mirati, miRNA Therapeutics, Molecular Templates, National Institutes of Health, Navire, NiKang, Novartis, OncoMed, Oncorus, Oncothyreon, Poseida, Precision Oncology, Prelude, PureTech, Pyramid, RasCal, Regeneron, Relay, Rgenix, Ribon, Samumed, Sapience, Seagen, Silicon, Simcha, Sirnaomics, Strategia, Syndax, Synthorx\/Sanofi, Taiho, Takeda, Tallac, Tarveda, Teneobio, Tesaro, Tocagen, Turning Point, U.T. MD Anderson Cancer Center, Vegenics, Xencor, Zhuhai Yufan.JSW reports consulting fees from Kanaph Therapeutics; speaker fees from AstraZeneca and Eisai; Advisory Board participation for BioNTech, Stemline\/Menarini, and Janssen; and research funding to the institution from multiple Biotech and Pharmaceutical companies to conduct industry sponsored oncology clinical trials.DL reports grants or contracts from Brooklyn, Immunotherapeutics, and AstraZeneca; and consulting fees from Adagene, Advanced Accelerator Applications, Bayer, Coherus, Eisai, Exelixis, Genentech, Ipsen Biopharmaceuticals, Lexicon, Merck, MiNA Therapeutics, QED, Servier, Sun Pharma, Taiho, DelCath, and TerSera Therapeutics.MWS reports no conflict of interest.ASP reports stock and other ownership interests in Actinum, Aptose, Alexion Pharmaceutical and Lyn Health; honoraria from Cardinal Health; consulting or advisory role for Amgen, Bristol, Meyers Squibb, Eisai, Ispen, Advanced Accelerator Applications, Incyte, Exelixis, Pfizer, QED Therapeutics, Lilly, Mirati, HUTCHMED International Corporation, and Astellas Pharma; speaker bureau participation for Ideo Oncology; research funding for the institution from Ispen, Bristol Meyers Squib, Exelixis, HUTCHMED International Corporation, Taiho Pharmaceuticals, Lilly, AstraZeneca, Incyte, Deciphera, G1 Therapeutics, Zentalis, Tempus, Camurus, Relay Therapeutics, Nucana, Merck, Surface, and Bayer; and travel accommodations, expenses from Pfizer.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}