2024
A phase Ib/II study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients (pts) with solid tumors harboring the 1q21.3 copy number amplification (CNA).
Lim J, Aau M, Yeong J, Goh B, Yong W, Soo R, Wong A, Tan D, Chee C, Sundar R, Jeyasekharan A, Wong C, Chen P, Liu H, Yu Q, Tam W, Lee S. A phase Ib/II study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients (pts) with solid tumors harboring the 1q21.3 copy number amplification (CNA). Journal Of Clinical Oncology 2024, 42: 43-43. DOI: 10.1200/jco.2024.42.23_suppl.43.Peer-Reviewed Original ResearchProgression-free survivalT cell populationsCD8+ T cell populationsCopy number amplificationInterleukin-1 receptor-associated kinase 1Solid tumorsTumor microenvironmentCell populationsDose levelsCD4+ T cell populationRecommended phase II dosePlasma cell-free DNAPeripheral blood mononuclear cells analysisSystemic immune modulationPhase II doseRefractory solid tumorsPhase Ib/II clinical trialDose-expansion cohortDendritic cell populationsMyeloid cell populationsTumor biopsy samplesImmune cell populationsDecreased tumor growthModulated immune cell populationsPreclinical animal modelsAbstract 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 escalationEfficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review
Shitara K, Falcone A, Fakih M, George B, Sundar R, Ranjan S, Van Cutsem E. Efficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review. The Oncologist 2024, 29: e601-e615. PMID: 38366864, PMCID: PMC11067808, DOI: 10.1093/oncolo/oyae007.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerRefractory metastatic colorectal cancerAdverse eventsDiscontinuation rate due to adverse eventsColorectal cancerChemorefractory metastatic colorectal cancerSafety outcomesMedian overall survivalSafety of FTD/TPIProgression-free survivalAdvanced solid tumorsAssociated with improved outcomesEarly-phase studiesSystematic reviewOverall survivalFTD/TPIRetrospective studySolid tumorsBevacizumabClinical efficacyTargeted agentsTumor typesAntineoplastic agentsAdvanced cancerImprove outcomes
2023
A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies
Chee C, Ooi M, Lee S, Sundar R, Heong V, Yong W, Ng C, Wong A, Lim J, Tan D, Soo R, Tan J, Yang S, Thura M, Al-Aidaroos A, Chng W, Zeng Q, Goh B. A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies. Targeted Oncology 2023, 18: 391-402. PMID: 37060431, PMCID: PMC10192144, DOI: 10.1007/s11523-023-00962-w.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAdvanced solid tumorsFirst-in-human studyEuropean Leukemia NetworkSolid tumorsHematologic malignanciesTreatment-emergent adverse eventsHuman antibodiesDose-escalation cohortsDose-limiting toxicityGrade 2 vomitingPRL-3Refractory solid tumorsResponse Evaluation CriteriaSolid tumor patientsDose-expansion cohortReduced tumor growthFirst-in-humanPhase IStable diseaseStoma outputEvaluation CriteriaMyeloid leukemiaPharmacodynamic relationshipsAdverse eventsClinical 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 scoresScoresClinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.
Lee M, Peng S, Lee A, Wong S, Tay R, Li J, Tariq A, Goh C, Tan Y, Tan B, Teo C, Chan E, Ooi M, Chng W, Chee C, Ho C, Walsh R, Wong M, Su Y, Alexander L, Sethi S, Tan S, Chan Y, Tan K, Lee S, Chai L, Sundar R. Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients. Annals, Academy Of Medicine, Singapore 2023, 52: 8-16. PMID: 36730801, DOI: 10.47102/annals-acadmedsg.2022302.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 mRNA vaccinesDoses of SARS-CoV-2 mRNA vaccinesMRNA vaccinesCancer patientsThird doseHaematological malignanciesLong-term immunogenicityCompared to patientsRisk of severe diseaseAnti-neoplastic treatmentActive cancer therapyVirus neutralisation assaySARS-CoV-2 infectionSystemic chemotherapyNo patientEarly administrationSeroconversion ratesVaccine immunogenicitySolid tumorsClinical efficacyClinical outcomesSevere infectionsCancer therapyHumoral responseActive treatment
2022
PRECISE CURATE.AI: A prospective feasibility trial to dynamically modulate personalized chemotherapy dose with artificial intelligence.
Blasiak A, Truong A, Tan W, Kumar K, Tan S, Teo C, Tan B, Tadeo X, Tan H, Chee C, Yong W, Ho D, Sundar R. PRECISE CURATE.AI: A prospective feasibility trial to dynamically modulate personalized chemotherapy dose with artificial intelligence. Journal Of Clinical Oncology 2022, 40: 1574-1574. DOI: 10.1200/jco.2022.40.16_suppl.1574.Peer-Reviewed Original ResearchStandard-of-careSingle-agent capecitabineCapecitabine doseProspective feasibility trialClinical trialsChemotherapy doseSolid tumorsImprove patient response ratesDosing decisionsTreatment of solid tumorsIndividualize chemotherapy dosingAdvanced solid tumorsProspective clinical trialPatient response rateRandomized clinical trialsPrescribed dosePatient-specific variationsOpen-labelDosing recommendationsTumor markersOrgan dysfunctionPatient comorbiditiesDose selectionOncological indicationsCapecitabinePhase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors
Lee M, Wong A, Ow S, Sundar R, Tan D, Soo R, Chee C, Lim J, Yong W, Lim S, Goh B, Wang L, Lee S. Phase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors. Targeted Oncology 2022, 17: 141-151. PMID: 35195837, PMCID: PMC8995271, DOI: 10.1007/s11523-022-00867-0.Peer-Reviewed Original ResearchConceptsHER2+ metastatic breast cancerDose-limiting toxicityMetastatic breast cancerBreast cancerSubcutaneous trastuzumabSolid tumorsConclusionsThe recommended phase II dosePharmacokinetic analysisRecommended phase II doseHER2+ breast cancerAdvanced solid tumorsPalliative systemic therapyMetastatic solid tumorsResultsThirty-seven patientsArea under the curveWeekly paclitaxelNeoadjuvant therapyStable diseaseFebrile neutropeniaPartial responseSystemic therapyMethodsEligible patientsEfficacy signalsElectrolyte disturbancesBiliary tract
2021
Abstract CT211: Personalized, rational, efficacy-driven chemotherapy dosing via an artificial intelligence system (PRECISE): A protocol for the PRECISE CURATE.AI pilot clinical trial
Teo C, Tan B, Tadeo X, Peng S, Soh H, Du S, Luo V, Bandla A, Sundar R, Ho D, Kee T, Blasiak A. Abstract CT211: Personalized, rational, efficacy-driven chemotherapy dosing via an artificial intelligence system (PRECISE): A protocol for the PRECISE CURATE.AI pilot clinical trial. Cancer Research 2021, 81: ct211-ct211. DOI: 10.1158/1538-7445.am2021-ct211.Peer-Reviewed Original ResearchTumor marker levelsRandomized controlled trialsChemotherapy doseSolid tumorsDrug doseDosing recommendationsMarker levelsAmerican Association for Cancer Research annual meetingsSignificant dose changesTumor marker measurementsCapecitabine-based chemotherapyMetastatic solid tumorsOptimal chemotherapy dosingRecruitment of patientsFrequent toxicitiesOpen-labelCA19-9Dose changesCohort expansionTumor markersSingle-armSuboptimal efficacyProportion of participantsChemotherapySerial measurementsPersonalised, Rational, Efficacy-Driven Cancer Drug Dosing via an Artificial Intelligence SystEm (PRECISE): A Protocol for the PRECISE CURATE.AI Pilot Clinical Trial
Tan B, Teo C, Tadeo X, Peng S, Soh H, Du S, Luo V, Bandla A, Sundar R, Ho D, Kee T, Blasiak A. Personalised, Rational, Efficacy-Driven Cancer Drug Dosing via an Artificial Intelligence SystEm (PRECISE): A Protocol for the PRECISE CURATE.AI Pilot Clinical Trial. Frontiers In Digital Health 2021, 3: 635524. PMID: 34713106, PMCID: PMC8521832, DOI: 10.3389/fdgth.2021.635524.Peer-Reviewed Original ResearchTumor marker levelsRandomised controlled trialsDrug dosePersonalised dosingSolid tumorsMarker levelsNational Healthcare GroupSignificant dose changesCapecitabine-based chemotherapyMetastatic solid tumorsDose of drugOpen-labelChemotherapy doseDose changesDosing recommendationsCohort expansionSingle-armSuboptimal efficacyProportion of participantsPrimary outcomeSecondary outcomesInterim analysisPhysician adherenceControlled trialsPrecision oncology
2020
A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid tumours
Ang Y, Ho G, Soo R, Sundar R, Tan S, Yong W, Ow S, Lim J, Chong W, Soe P, Tai B, Wang L, Goh B, Lee S. A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid tumours. BMC Cancer 2020, 20: 1118. PMID: 33203399, PMCID: PMC7672922, DOI: 10.1186/s12885-020-07616-4.Peer-Reviewed Original ResearchConceptsProgression-free-survivalAdvanced solid tumorsBreast cancer patientsSolid tumorsCancer patientsMedian progression-free-survivalRandomized phase II trialMetastatic breast cancer patientsClinical-benefit rateProphylactic G-CSFNon-haematological toxicityPrimary tumor siteAdministration of sunitinibPhase II trialAdvanced solid cancersMedian OSHaematological toxicityDoxorubicin-cyclophosphamideTrial registrationThe studyII trialNeutrophil nadirPrimary endpointSecondary endpointsG-CSFIntermittent administration
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
Clinical outcomes of adolescents and young adults with advanced solid tumours participating in phase I trials
Sundar R, McVeigh T, Dolling D, Petruckevitch A, Diamantis N, Ang J, Chenard-Poiriér M, Collins D, Lim J, Ameratunga M, Khan K, Kaye S, Banerji U, Lopez J, George A, de Bono J, van der Graaf W. Clinical outcomes of adolescents and young adults with advanced solid tumours participating in phase I trials. European Journal Of Cancer 2018, 101: 55-61. PMID: 30025230, DOI: 10.1016/j.ejca.2018.06.003.Peer-Reviewed Original ResearchConceptsPhase I trialPhase I clinical trialAdvanced solid tumorsI trialOverall survivalAYA patientsSolid tumorsCancer syndromesCohort of AYA patientsMolecular characterisation of tumoursOutcomes of AYA patientsClinical benefit rateMedian overall survivalOutcomes of AYAsSomatic genetic aberrationsSignificant family historyRoyal Marsden HospitalHereditary cancer syndromesCharacterisation of tumoursTherapeutic treatment optionsClinical outcomes of adolescentsClinical trial dataDrug Development UnitYoung adultsGenetic aberrationsThe role of genomic profiling in adolescents and young adults (AYAs) with advanced cancer participating in phase I clinical trials
McVeigh T, Sundar R, Diamantis N, Kaye S, Banerji U, Lopez J, de Bono J, van der Graaf W, George A. The role of genomic profiling in adolescents and young adults (AYAs) with advanced cancer participating in phase I clinical trials. European Journal Of Cancer 2018, 95: 20-29. PMID: 29614442, PMCID: PMC6296443, DOI: 10.1016/j.ejca.2018.02.028.Peer-Reviewed Original ResearchConceptsDrug Development UnitGermline testingAdvanced cancerPhase I clinical trialTumor testingPersonal history of cancerAdvanced solid tumorsProportion of AYAsRoyal Marsden HospitalHistory of cancerAt-risk relativesCommon cancer typesYoung adultsDepartmental databaseClinicopathological featuresSolid tumorsChart reviewFamily risk factorsGermline mutationsPathogenic variantsStudy cohortCancer predispositionGenomic profilingPatient managementGenetic testing
2017
Abstract 3807: ATM protein loss and clinical outcomes with platinum chemotherapy in patients with advanced solid tumors
Sundar R, Miranda S, Carreira S, Chénard-Poirier M, Rodrigues D, Figueiredo I, Bertan C, Yuan W, Perez D, Ferreira A, Tunariu N, Mateo J, Bono J. Abstract 3807: ATM protein loss and clinical outcomes with platinum chemotherapy in patients with advanced solid tumors. Cancer Research 2017, 77: 3807-3807. DOI: 10.1158/1538-7445.am2017-3807.Peer-Reviewed Original ResearchATM protein lossAdvanced solid tumorsPlatinum chemotherapyPlatinum therapyATM lossClinical outcomesMetastatic sitesATM mutationsIHC lossSolid tumorsNext generation sequencingAmerican Association for Cancer Research annual meetingsSensitivity to platinum therapySomatic ATM mutationsAdvanced solid cancersSites of patientsNuclear staining intensityRabbit monoclonal antibodyLoss of ATM expressionProtein lossColorectal cancer cohortDNA damage repair signalingTP53 mutationsArchival tumorsH-scoreClinical 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
2015
Nivolumab in NSCLC: latest evidence and clinical potential
Sundar R, Cho B, Brahmer J, Soo R. Nivolumab in NSCLC: latest evidence and clinical potential. Therapeutic Advances In Medical Oncology 2015, 7: 85-96. PMID: 25755681, PMCID: PMC4346216, DOI: 10.1177/1758834014567470.Peer-Reviewed Original ResearchNon-small cell lung cancerStudy of nivolumabImmune checkpoint modulatorsPD-1 inhibitorsCell lung cancerMolecular targeted therapyTreatment of patientsEarly phase studiesHost immune responseUnresectable melanomaPD-1Checkpoint modulatorsSolid tumorsNivolumabEvading host immune responsesImmune modulationLung cancerImmune responseClinical potentialImmune systemLigand pathwayRegulatory approvalTumorPatientsChemotherapy