2024
A phase Ib/II study of an anti-CD137 agonist antibody ADG106 in combination with weekly paclitaxel and dose-dense doxorubicin/cyclophosphamide.
Lee M, Ow S, Wong A, Lim S, Lim J, Soo R, Cheng Ean C, Tan D, Yong W, Chan G, Ho J, Sooi K, Low Q, Ang C, Cheo S, Sundar R, Goh B, Lee S. A phase Ib/II study of an anti-CD137 agonist antibody ADG106 in combination with weekly paclitaxel and dose-dense doxorubicin/cyclophosphamide. Journal Of Clinical Oncology 2024, 42: e14507-e14507. DOI: 10.1200/jco.2024.42.16_suppl.e14507.Peer-Reviewed Original ResearchAdverse eventsG3 neutropeniaTumor biopsiesWeekly PPeripheral neuropathyHER2 negative breast cancer patientsPhase IbDose levelsRecommended phase 2 doseAll-grade adverse eventsNegative breast cancer patientsMatched tumor biopsiesPhase 2 doseTumor immune markersPneumocystis jiroveci pneumoniaAdvanced solid tumorsPalliative systemic therapyPhase Ib trialPhase II trialPhase IISerial tumor biopsiesBreast cancer patientsIgG4 monoclonal antibodyAcneiform rashAnti-CD137
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 biopsies
2020
Integration of Antiangiogenic Therapy with Cisplatin and Gemcitabine Chemotherapy in Patients with Nasopharyngeal Carcinoma
Chong W, Lim C, Sinha A, Tan C, Chan G, Huang Y, Kumarakulasinghe N, Sundar R, Jeyasekharan A, Loh W, Tay J, Yadav K, Wang L, Wong A, Kong L, Soo R, Lau J, Soon Y, Goh R, Ho F, Chong S, Lee S, Loh K, Tai B, Lim Y, Goh B. Integration of Antiangiogenic Therapy with Cisplatin and Gemcitabine Chemotherapy in Patients with Nasopharyngeal Carcinoma. Clinical Cancer Research 2020, 26: 5320-5328. PMID: 32816944, DOI: 10.1158/1078-0432.ccr-20-1727.Peer-Reviewed Original ResearchConceptsLocally advanced nasopharyngeal carcinomaAdvanced nasopharyngeal carcinomaNasopharyngeal carcinomaConcurrent chemoradiationGemcitabine chemotherapyArm CIncreased immune cell infiltrationComplete metabolic responsePosttreatment tumor biopsiesAnti-VEGF therapyArm A patientsRelapse-free survivalMetastatic nasopharyngeal carcinomaImmune cell infiltrationImmune cell traffickingVEGF axisTumor responseInduction cisplatinAntiangiogenic therapyTumor biopsiesTumor perfusionA patientsFDG-PETPericyte coverageStandard treatment
2019
463P Evaluation of pharmacodynamic (PD) biomarkers in advanced cancer patients treated with oxidative phosphorylation (OXPHOS) inhibitor, OPC-317 (OPC)
Eu J, Yadav K, Lim Y, Hirpara J, Kong L, Ng Z, Lee V, Lee S, Tan D, Soo R, Chee C, Yong W, Sundar R, Lim J, Wang L, Ohi N, Tsunoda T, Pervaiz S, Goh B, Wong A. 463P Evaluation of pharmacodynamic (PD) biomarkers in advanced cancer patients treated with oxidative phosphorylation (OXPHOS) inhibitor, OPC-317 (OPC). Annals Of Oncology 2019, 30: v174. DOI: 10.1093/annonc/mdz244.025.Peer-Reviewed Original ResearchMitochondrial membrane potentialSerum metabolomeHER2+ breast cancerOncogene-addicted tumorsDose-finding phaseClinically tolerable dosesCancer stem cellsNon-significant riseG3/4 toxicitiesOxidative phosphorylation inhibitionSignificantly with treatmentGIST patientsTolerated doseTumor biopsiesImmunohistochemistry expressionCopy numberOxidative phosphorylationSerum lactateBreast cancerClinical developmentDrug resistanceMerck SeronoDose levelsDay 1Pathway inhibitorA 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 studiesEpigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer
Sundar R, Huang K, Qamra A, Kim K, Kim S, Kang W, Tan A, Lee J, Tan P. Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer. Annals Of Oncology 2019, 30: 424-430. PMID: 30624548, PMCID: PMC6442650, DOI: 10.1093/annonc/mdy550.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionMetastatic gastric cancerT cell cytolytic activityResistance to immune checkpoint inhibitionCheckpoint inhibitionGastric cancerCytolytic activityImmune evasionMedian progression-free survivalPhase II clinical trial of patientsCancer treated with immunotherapyClinical trials of patientsMechanisms of immune evasionResponse rateTreated with pembrolizumabPhase II clinical trialProgression-free survivalFresh tumor biopsiesPost-treatment biopsiesCohort of patientsTrial of patientsEarly gastric cancerArchival tissue samplesClinical responseTumor biopsies