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This pilot first-in-human study characterized the safety, tolerability, and efficacy of SMK Therapy in subjects with advanced metastatic cancer. <jats:italic>Methods<\/jats:italic> All subjects (<jats:italic>n<\/jats:italic>\u2009=\u200930) received SMK Therapy for an initial 6\u00a0week\u00a0Cycle (5\u00a0days on, 2 off per week) and continued if well tolerated. Safety signals, clinical response, overall survival, progression free survival (PFS), and quality of life changes were assessed. <jats:italic>Results<\/jats:italic> The most common drug related adverse events were hyperpigmentation and rash. All drug related adverse events were mild to moderate in intensity. Following treatment with SMK Therapy, 4 subjects achieved complete response, 6 partial response, and 17 stable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (total clinical benefit 90%). Responses were observed within 6\u00a0weeks, and continued to improve, with 3 complete and 3 partial responders achieving best response after at least 3.2\u00a0months. Durable stable disease was observed, lasting a median duration of 11\u00a0months (range 1\u201331\u00a0months). Median overall survival for all subjects was 29.8\u00a0months, and median PFS was 13\u00a0months. Following 6\u00a0weeks of treatment, most (83.3%) subjects showed an improvement in Eastern Cooperative Oncology Group (ECOG) score and an improvement in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ 30) global health status (baseline 61.2\u2009\u00b1\u200925.0; end of Cycle 1 80.7\u2009\u00b1\u200914.7; <jats:italic>n<\/jats:italic>\u2009=\u200929; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). <jats:italic>Conclusions<\/jats:italic> The results of this study support continued development of SM-88.<\/jats:p>","DOI":"10.1007\/s10637-019-00758-8","type":"journal-article","created":{"date-parts":[[2019,3,30]],"date-time":"2019-03-30T08:02:30Z","timestamp":1553932950000},"page":"392-401","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A first-in-human study of the novel metabolism-based anti-cancer agent SM-88 in subjects with advanced metastatic cancer"],"prefix":"10.1007","volume":"38","author":[{"given":"Jeanetta","family":"Stega","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus S.","family":"Noel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Vandell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Stega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Del Priore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,30]]},"reference":[{"issue":"5930","key":"758_CR1","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1126\/science.1160809","volume":"324","author":"MG Vander Heiden","year":"2009","unstructured":"Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. 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