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-CD137Efficacy 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 events
2022
PRECISE CURATE.AI: A prospective feasibility trial to dynamically modulate personalized chemotherapy dose with artificial intelligence.
Blasiak A, Truong A, Jeit L, Kumar K, Tan S, Teo C, Tan B, Tadeo X, Tan L, 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
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 aberrationsVistusertib (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 trialThe 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 rate