2022
Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer.
Lim J, Wong A, Ow S, Ngoi N, Chan G, Ang Y, Chong W, Lim S, Lim Y, Lee M, Choo J, Tan H, Yong W, Soo R, Tan D, Chee C, Sundar R, Yadav K, Jain S, Wang L, Tai B, Goh B, Lee S. Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer. Clinical Cancer Research 2022, 28: 2248-2256. PMID: 35363275, DOI: 10.1158/1078-0432.ccr-21-4179.Peer-Reviewed Original ResearchConceptsBreast cancerDose expansionEstrogen receptorHormone receptor-positive breast cancerPhase II dose expansionRecommended phase II doseReceptor-positive breast cancerCDK4/6 inhibitor therapyDose-expansion studyPaired tumor biopsiesPhase Ib/II trialPhase II doseVascular normalization indexTreated with lenvatinibDose of lenvatinibER+/HER2- breast cancerMetastatic breast cancerPreliminary antitumor activityEstrogen-responsive genesLenvatinib combinationII doseMetastatic settingInhibitor therapyMultikinase inhibitorTumor biopsiesA phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies
Ho J, Heong V, Yong W, Soo R, Chee C, Wong A, Sundar R, Thian Y, Gopinathan A, Pang M, Koe P, Jeraj S, Soe P, Soe M, Tang T, Ng M, Tai D, Tan T, Xu H, Chang H, Landesman Y, Shah J, Shacham S, Lee S, Tan D, Goh B, Tan D. A phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies. Therapeutic Advances In Medical Oncology 2022, 14: 17588359221087555. PMID: 35432603, PMCID: PMC9008867, DOI: 10.1177/17588359221087555.Peer-Reviewed Original ResearchPhase 1 studyAsian patientsMetastatic malignancyMedian t<sub>max</sub> wasGrade 3 adverse eventsNCI Common Terminology CriteriaRecommended phase 2 doseAsian patient cohortContinuous dosing regimensGrade 3 fatiguePhase 2 doseThymic carcinoma patientsDose-escalation designCommon Terminology CriteriaInhibitor of nuclear exportCytoplasmic localization of p27Dose expansionComplete responseHodgkin lymphomaExpansion cohortLymphoma patientsPartial responseDrug holidayEscalation designPharmacodynamic assessments
2021
40P Phase I study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of selinexor in Asian patients with advanced solid tumour malignancies
Ho J, Heong V, Yong W, Soo R, Chee C, Wong A, Thian Y, Sundar R, Gopinathan A, Lee S, Goh B, Xu H, Tan D. 40P Phase I study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of selinexor in Asian patients with advanced solid tumour malignancies. Annals Of Oncology 2021, 32: s17. DOI: 10.1016/j.annonc.2021.01.055.Peer-Reviewed Original Research
2019
A phase Ib/II trial of lenvatinib (len) and letrozole (let) incorporating pharmacodynamics studies in postmenopausal women with hormone receptor positive (HR+) locally advanced/metastatic breast cancer (LABC/MBC).
Lim J, Wong A, Ow S, Eng L, Sundar R, Chan G, Yadav K, Heong V, Tan D, Soo R, Chee C, Yong W, Goh B, Lee S. A phase Ib/II trial of lenvatinib (len) and letrozole (let) incorporating pharmacodynamics studies in postmenopausal women with hormone receptor positive (HR+) locally advanced/metastatic breast cancer (LABC/MBC). Journal Of Clinical Oncology 2019, 37: 1045-1045. DOI: 10.1200/jco.2019.37.15_suppl.1045.Peer-Reviewed Original ResearchDose-limiting toxicityDisease control ratePalmar-plantar erythrodysesthesiaDose reductionBreast cancerDose levelsMechanisms of endocrine resistanceRecommended phase 2 dosePhase 2 doseAdvanced/metastatic breast cancerHR+ breast cancerPhase Ib trialContinuous daily dosingSerial tumor biopsiesAnti-tumor activityStandard of careDose expansionG3 toxicityPrior CTPostmenopausal womenTumor biopsiesEndocrine resistanceDaily doseEstrogen receptorPreclinical studies
2017
First-in-human phase I study of an oral HSP90 inhibitor, TAS-116, in advanced solid tumors.
Yanagitani N, Horiike A, Kitazono S, Ohyanagi F, Kondo S, Shimomura A, Fujiwara Y, Doi T, Kuboki Y, Kawazoe A, Shitara K, Ohno I, Banerji U, Sundar R, Ohkubo S, Huang J, Nishio M, Yamamoto N. First-in-human phase I study of an oral HSP90 inhibitor, TAS-116, in advanced solid tumors. Journal Of Clinical Oncology 2017, 35: 2546-2546. DOI: 10.1200/jco.2017.35.15_suppl.2546.Peer-Reviewed Original ResearchTAS-116Solid tumorsFirst-in-human phase I studyAntitumor activityOral HSP90 inhibitorAccelerated titration designPhase 2 studyPhase I studyPreliminary antitumor activityPhase 1 studyEvidence of target engagementDose expansionFlat doseEscalating dosesDose proportionalityRepeated administrationQD scheduleSafety profileEye disordersIncreased creatinineAdverse eventsTitration designDays administrationNon-purinePatients