2019
First-in-human phase I study of an oral HSP90 inhibitor, TAS-116, in patients with advanced solid tumors
Shimomura A, Yamamoto N, Kondo S, Fujiwara Y, Suzuki S, Yanagitani N, Horiike A, Kitazono S, Ohyanagi F, Doi T, Kuboki Y, Kawazoe A, Shitara K, Ohno I, Banerji U, Sundar R, Ohkubo S, Calleja E, Nishio M. First-in-human phase I study of an oral HSP90 inhibitor, TAS-116, in patients with advanced solid tumors. Molecular Cancer Therapeutics 2019, 18: molcanther.0831.2018. PMID: 30679388, DOI: 10.1158/1535-7163.mct-18-0831.Peer-Reviewed Original ResearchConceptsGastrointestinal stromal tumorsPreliminary antitumor efficacyDose-escalation phaseAdvanced solid tumorsSolid tumorsTAS-116Eye disordersEscalation phaseFirst-in-human phase I studyPretreated gastrointestinal stromal tumoursHsp90 inhibitorsTreatment-related adverse eventsNon-small cell lung cancerFirst-in-human studyOral HSP90 inhibitorPhase I studyCell lung cancerPartial responseStromal tumorsDose proportionalityAntitumor efficacySafety profileSystemic exposureAdverse eventsLung cancer
2018
Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer
Basu B, Krebs M, Sundar R, Wilson R, Spicer J, Jones R, Brada M, Talbot D, Steele N, Garces A, Brugger W, Harrington E, Evans J, Hall E, Tovey H, de Oliveira F, Carreira S, Swales K, Ruddle R, Raynaud F, Purchase B, Dawes J, Parmar M, Turner A, Tunariu N, Banerjee S, de Bono J, Banerji U. Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer. Annals Of Oncology 2018, 29: 1918-1925. PMID: 30016392, PMCID: PMC6158767, DOI: 10.1093/annonc/mdy245.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBenzamidesCarcinoma, Non-Small-Cell LungDrug Administration ScheduleFemaleHumansLung NeoplasmsMaleMaximum Tolerated DoseMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Middle AgedMorpholinesOvarian NeoplasmsPaclitaxelPhosphorylationProtein Kinase InhibitorsPyrimidinesResponse Evaluation Criteria in Solid TumorsRibosomal Protein S6 KinasesConceptsHigh-grade serous ovarian cancerSquamous non-small-cell lung cancerNon-small-cell lung cancerWeekly paclitaxelOvarian cancerSchedule ALung cancerIntermittent scheduleRecommended phase II doseResponse rateDose-escalated armPhase II doseRECIST response rateDose-limiting toxicityProgression-free survivalAdvanced solid tumorsPhase I trialSerous ovarian cancerResistance to chemotherapyP-S6K levelsConsecutive daysII doseDose escalationExpansion cohortI trial