2024
CHAPTER-GIST-101: A phase I study of pimitespib combined with imatinib in patients with imatinib-refractory gastrointestinal stromal tumor.
Hirano H, Naito Y, Sundar R, Komatsu Y, Kurokawa Y, Li J, Ozaka M, Iwatsuki M, Chen J, Yen C, Zalcberg J, Roy A, Chen L, Nishida T, Doi T. CHAPTER-GIST-101: A phase I study of pimitespib combined with imatinib in patients with imatinib-refractory gastrointestinal stromal tumor. Journal Of Clinical Oncology 2024, 42: tps97-tps97. DOI: 10.1200/jco.2024.42.23_suppl.tps97.Peer-Reviewed Original ResearchDose-escalation partGastrointestinal stromal tumorsProgression-free survivalDays on/2 daysResistance to IMStromal tumorsImatinib-refractory gastrointestinal stromal tumorsInvestigator-assessed progression-free survivalAdvanced gastrointestinal stromal tumorsKinase-domain mutationsOvercome IM resistanceWeeks on/2 weeksDisease control rateDose-limiting toxicitySecond-line settingDuration of responseMaximum tolerated dosePhase I studyPhase 3 studyPhase 1 studySoft tissue sarcomasHsp90 inhibitorsInhibited tumor growthAnti-tumor activityOverall survivalAbstract CT160: A phase I trial to evaluate allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells in subjects with advanced solid tumors or hematological malignancies (the ANGELICA Trial)
Choo J, Tan W, Luk L, Zeng J, Soh T, Soon S, Lieow J, Wong C, Pang M, Bari S, Poon M, Koh L, Chng W, Jeyasekharan A, Tan L, Chan E, Sundar R. Abstract CT160: A phase I trial to evaluate allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells in subjects with advanced solid tumors or hematological malignancies (the ANGELICA Trial). Cancer Research 2024, 84: ct160-ct160. DOI: 10.1158/1538-7445.am2024-ct160.Peer-Reviewed Original ResearchAdoptive cellular therapyPhase I studyHematologic malignanciesSolid tumorsCellular infusionT cellsHealthy donorsAmerican Association for Cancer Research annual meetingsDose levelsRecommended phase 2 doseTreatment of hematological malignanciesPhase 2 dosePoor marrow functionSubcutaneous IL-2Treatment-refractory tumorsDose-limiting toxicityPeripheral blood mononuclear cellsPre-treated patientsT-cell therapyPre-clinical dataBlood mononuclear cellsT cell survivalEnrollment of patientsDiverse tissue originDose escalation
2023
Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials
Loh J, Wu J, Chieng J, Chan A, Yong W, Sundar R, Lee S, Wong A, Lim J, Tan D, Soo R, Goh B, Tai B, Chee C. Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials. British Journal Of Cancer 2023, 128: 1514-1520. PMID: 36797357, PMCID: PMC10070409, DOI: 10.1038/s41416-023-02193-2.Peer-Reviewed Original ResearchConceptsNeutrophil-lymphocyte ratioRoyal Marsden HospitalPhase I studyPhase I clinical trialPoor ECOG statusPre-treated patientsPrimary tumor sitePhase I populationLonger-term survivalECOG statusPrognostic factorsPrognostic scoreRetrospective reviewTumor siteAsian patientsSolid tumorsClinical outcomesPoor prognosisBackgroundPatient selectionPrognostic abilityPrognostic modelPatientsPrognosisIncreased scoresScores
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
2020
PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases
Kim G, Tan L, Sundar R, Lieske B, Chee C, Ho J, Shabbir A, Babak M, Ang W, Goh B, Yong W, Wang L, So J. PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases. Clinical Cancer Research 2020, 27: 1875-1881. PMID: 33148667, DOI: 10.1158/1078-0432.ccr-20-2152.Peer-Reviewed Original ResearchConceptsPressurized intraperitoneal aerosol chemotherapyPressurized intraperitoneal aerosolized chemotherapy proceduresPeritoneal cancer indexPeritoneal metastasisAerosol chemotherapyMedian peritoneal cancer indexPeritoneal Regression Grading ScoreRecommended phase II doseGrade 2 pancreatitisHighest-dose cohortPhase II doseDose-limiting toxicityFirst-line chemotherapyDose-escalation designTreat peritoneal metastasisPhase I studyImprove drug distributionII doseStable diseaseCancer indexMedian ageCohort expansionGastrointestinal tumorsPharmacokinetic analysisDose levelsSafety, pharmacokinetics and tissue penetration of PIPAC paclitaxel in a swine model
Tan H, Kim G, Charles C, Li R, Jang C, Shabbir A, Chue K, Tai C, Sundar R, Goh B, Bonney G, Looi W, Cheow E, So J, Wang L, Yong W. Safety, pharmacokinetics and tissue penetration of PIPAC paclitaxel in a swine model. European Journal Of Surgical Oncology 2020, 47: 1124-1131. PMID: 32800400, DOI: 10.1016/j.ejso.2020.06.031.Peer-Reviewed Original ResearchConceptsSolvent-based paclitaxelAdverse eventsGrade 2 hypersensitivity reactionSystemic exposure to paclitaxelAbsolute neutrophil countExposure to paclitaxelPhase I studyShort-term safetySignificant adverse eventsTissue drug concentrationsConcentrations of paclitaxelPotential adverse eventsYorkshire x Landrace pigsPeritoneal carcinomatosisPeritoneal biopsiesNeutrophil countPeritoneal surfaceToxicity profileBlood countIV infusionPeritoneal cavityPharmacokinetic analysisClinical trialsHigh dosesPharmacokinetic comparisonMolecular profiling of metastatic breast cancer (MBC) and target-based therapeutic matching in an Asian tertiary phase I oncology unit.
Walsh R, Ngoi N, Ong R, Ow S, Wong A, Eng L, Lim Y, Heong V, Sundar R, Soo R, Yong W, Chee C, Goh B, Lee S, Tan D, Lim J. Molecular profiling of metastatic breast cancer (MBC) and target-based therapeutic matching in an Asian tertiary phase I oncology unit. Journal Of Clinical Oncology 2020, 38: 3561-3561. DOI: 10.1200/jco.2020.38.15_suppl.3561.Peer-Reviewed Original ResearchMedian progression free survivalTriple negative breast cancerPhase I unitMolecular profilingEndocrine therapyNext generation sequencingBreast cancerClinical benefit rateProgression free survivalMetastatic breast cancerPhase I studyTumor molecular profilingNegative breast cancerNext generation sequencing findingsPIK3CA E542KPan-FGFR inhibitorMatched PTPIK3CA H1047RFree survivalMBC patientsMetastatic sitesI unitsFGFR pathwayTertiary centreTumor subtypes
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
P1.01-38 A Phase II With a Lead-In Phase I Study to Examine Safety and Efficacy of Hydroxychloroquine and Gefitinib in Advanced NSCLC
Huang Y, Wong A, Soo R, Soh T, Pang A, Tan C, Ling W, Voon P, Lim J, Sundar R, Kumarakulasinghe N, Lim H, Goh B, Chin T. P1.01-38 A Phase II With a Lead-In Phase I Study to Examine Safety and Efficacy of Hydroxychloroquine and Gefitinib in Advanced NSCLC. Journal Of Thoracic Oncology 2018, 13: s474-s475. DOI: 10.1016/j.jtho.2018.08.594.Peer-Reviewed Original Research
2017
Clinical outcomes of adolescents and young adults (AYA) with advanced solid tumors participating in phase I trials.
Sundar R, McVeigh T, Petruckevitch A, Diamantis N, Ang J, Chenard-Poirier M, Collins D, Lim J, Ameratunga M, Khan K, Kaye S, Banerji U, Lopez J, De Bono J, Van Der Graaf W. Clinical outcomes of adolescents and young adults (AYA) with advanced solid tumors participating in phase I trials. Journal Of Clinical Oncology 2017, 35: 10536-10536. DOI: 10.1200/jco.2017.35.15_suppl.10536.Peer-Reviewed Original ResearchPhase I trialAdvanced solid tumorsPhase I studyAYA patientsI trialFamily historySolid tumorsDrug Development UnitClinical outcomesOutcomes of AYA patientsMedian progression free survivalMolecular characterization of tumorsClinical benefit rateProgression free survivalSomatic genetic aberrationsRoyal Marsden HospitalHereditary cancer syndromesClinical outcomes of adolescentsCharacterization of tumorsMedian OSSystemic chemotherapyFree survivalGenetic aberrationsPredictive biomarkersBenefit rateFirst-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
2016
362PD TAX-TORC: An investigator initiated phase I study combining the dual mTORC1/2 inhibitor AZD2014 in combination with weekly paclitaxel in high-grade serous ovarian cancer
Banerji U, Basu B, Spicer J, Wilson R, Hall E, Sundar R, Kumar S, Wu Y, Coyle V, Carreira S, Parmar M, Dawes J, Banerjee S, de Bono J. 362PD TAX-TORC: An investigator initiated phase I study combining the dual mTORC1/2 inhibitor AZD2014 in combination with weekly paclitaxel in high-grade serous ovarian cancer. Annals Of Oncology 2016, 27: vi115. DOI: 10.1093/annonc/mdw368.05.Peer-Reviewed Original Research
2015
Phase I study of the safety and tolerability of the Exportin 1 (XPO1) inhibitor Selinexor (SXR) in Asian patients (pts) with advanced solid cancers.
Tan D, Pang M, Yong W, Soo R, Chee C, Thian Y, Gopinathan A, Wong A, Koe P, Sundar R, Ho J, Friedlander S, Landesman Y, Rashal T, McCauley D, Shacham S, Lee S, Goh B. Phase I study of the safety and tolerability of the Exportin 1 (XPO1) inhibitor Selinexor (SXR) in Asian patients (pts) with advanced solid cancers. Journal Of Clinical Oncology 2015, 33: 2542-2542. DOI: 10.1200/jco.2015.33.15_suppl.2542.Peer-Reviewed Original Research