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
Phase II study of trifluridine/tipiracil (FTD/TPI) in HER2-negative metastatic breast cancers with or without prior exposure to fluoropyrimidines.
Lim J, Ow S, Wong A, Lee M, Chan G, Low J, Sundar R, Choo J, Tai B, Lee S. Phase II study of trifluridine/tipiracil (FTD/TPI) in HER2-negative metastatic breast cancers with or without prior exposure to fluoropyrimidines. Journal Of Clinical Oncology 2023, 41: 1099-1099. DOI: 10.1200/jco.2023.41.16_suppl.1099.Peer-Reviewed Original ResearchObjective response rateMetastatic breast cancerProgression-free survivalPhase II studyLead-in phaseCohort ADose modificationBreast cancerDetermination of progression-free survivalSingle arm phase II studyHER2-negative metastatic breast cancerConsistent with known toxicitiesMedian progression-free survivalTreatment-related adverse eventsResponse rateDose-confirmation phaseEvents of neutropeniaTreated with FTD/TPIClinical benefit rateDose-limiting toxicityOral drug combinationsTreatment of patientsAnti-tumor activityThymidine phosphorylase inhibitorMetastatic settingA 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
Phase 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
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 and tolerability of oxaliplatin based pressurized intraperitoneal aerosol chemotherapy (PIPAC) for patients with peritoneal carcinomatosis: A phase I dose-finding study in Asian patients.
Sundar R, Kim G, Tan H, Wang L, Chue K, Tai C, Teo S, Jang C, Chee C, Lieske B, Chee C, Shabbir A, So J, Yong W. Safety and tolerability of oxaliplatin based pressurized intraperitoneal aerosol chemotherapy (PIPAC) for patients with peritoneal carcinomatosis: A phase I dose-finding study in Asian patients. Journal Of Clinical Oncology 2020, 38: 360-360. DOI: 10.1200/jco.2020.38.4_suppl.360.Peer-Reviewed Original ResearchPressurized intraperitoneal aerosol chemotherapyPeritoneal carcinomatosis indexDose-limiting toxicityHyperthermic intraperitoneal chemotherapyPhase 1 studyDose cohortsAsian patientsDose-escalation phase 1 studyPIPAC administrationsGrade 3 adverse eventsMedian peritoneal carcinomatosis indexPeritoneal carcinomatosis index scoreRecommended phase 2 dosePressurized intraperitoneal aerosolized chemotherapy proceduresFailure of standard therapyPhase I dose-finding studyGastrointestinal primary tumorsHighest dose cohortPhase 2 doseDose-escalation studyIntraperitoneal chemotherapyPeritoneal carcinomatosisEscalation studyPeritoneal metastasisOxaliplatin chemotherapy
2019
Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy
Bandla A, Tan S, Kumarakulasinghe N, Huang Y, Ang S, Magarajah G, Hairom Z, Lim J, Wong A, Chan G, Ngoi N, Ang E, Lee Y, Chan A, Lee S, Thakor N, Wilder-Smith E, Sundar R. Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy. Supportive Care In Cancer 2019, 28: 3691-3699. PMID: 31811482, PMCID: PMC7316694, DOI: 10.1007/s00520-019-05177-2.Peer-Reviewed Original ResearchConceptsNerve conduction studiesTotal Neuropathy ScoreFrozen glovesTaxane chemotherapyNeuropathy scorePeripheral neuropathyDose-limiting toxicityConcomitant with chemotherapyTaxane-induced peripheral neuropathySeverity of neuropathySensory nerve amplitudesPrevention of neurotoxicitySkin temperature reductionLimb hypothermiaMonths post-chemotherapyPaclitaxel chemotherapyNerve amplitudeMotor amplitudeSevere neuropathyPost-chemotherapyUndesired side effectsChemotherapyCancer patientsNeuropathySide effectsA 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
2018
Vistusertib (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 trialA phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer
Sundar R, Rha S, Yamaue H, Katsuda M, Kono K, Kim H, Kim C, Mimura K, Kua L, Yong W. A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer. BMC Cancer 2018, 18: 332. PMID: 29587677, PMCID: PMC5870101, DOI: 10.1186/s12885-018-4234-8.Peer-Reviewed Original ResearchConceptsAdvanced gastric cancerCytotoxic T lymphocytesGastric cancerCancer vaccinesOverall survivalAdverse eventsRecommended phase 2 doseMedian progression free survivalSpecific cytotoxic T lymphocytesTreatment-related adverse eventsAdvanced gastric cancer patientsPeptide cancer vaccinesPhase 2 dosePhase I/Ib studyPositive CTL responsesDose-limiting toxicityMedian overall survivalProgression free survivalInjection site erythemaOptimal dosing scheduleGastric cancer patientsSingle-arm trialPhase I/IbStable diseaseFree survival
2017
Abstract 3081: Precision medicine for patients with advanced small cell lung cancer treated with novel therapeutic agents in a phase I clinical trials unit
Lim J, Harris S, Ameratunga M, Sundar R, Ang J, Collins D, Chénard-Poirier M, Garces A, Kaye S, Lopez J, Banerji U, Bono J, Yap T. Abstract 3081: Precision medicine for patients with advanced small cell lung cancer treated with novel therapeutic agents in a phase I clinical trials unit. Cancer Research 2017, 77: 3081-3081. DOI: 10.1158/1538-7445.am2017-3081.Peer-Reviewed Original ResearchSmall cell lung cancerAdvanced small cell lung cancerNovel therapeutic agentsRECIST SDStable diseasePD-1Partial responsePARP inhibitorsNovel therapiesAmerican Association for Cancer Research annual meetingsNext generation sequencingTherapeutic agentsSignals of antitumor activityNo dose limiting toxicitiesDNA damage repairClinical outcomes of patientsResponse to novel therapiesPD-1 inhibitorsPlatinum-sensitive diseaseRECIST partial responseRECIST stable diseaseDose-limiting toxicityTargeted next generation sequencingTumor molecular profilingPhase I trialTAX-TORC: A phase I trial of vistusertib (AZD2014) in combination with weekly paclitaxel with integrated pharmacodynamic (PD) and molecular characterization (MC) studies.
Sundar R, Basu B, Wilson R, Spicer J, Jones R, Krebs M, Brada M, Talbot D, Steele N, Hall E, Tovey H, Carreira S, de Oliveira F, Swales K, Balarajah G, Dawes J, Parmar M, De Bono J, Banerji U. TAX-TORC: A phase I trial of vistusertib (AZD2014) in combination with weekly paclitaxel with integrated pharmacodynamic (PD) and molecular characterization (MC) studies. Journal Of Clinical Oncology 2017, 35: 2571-2571. DOI: 10.1200/jco.2017.35.15_suppl.2571.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerHigh-grade serous ovarian cancer patientsRecommended phase 2 doseMedian progression free survivalImproving outcomes of patientsPhase 2 doseDose-limiting toxicityDose-escalation partProgression free survivalArchival tumor tissuePhase I trialSerous ovarian cancerOutcomes of patientsLines of treatmentResistance to chemotherapyP-S6K levelsPre-dose levelsPlatelet-rich plasmaWeekly paclitaxelExpansion cohortFree survivalPlatinum therapyATM mutationsLimiting toxicitiesBID POLimb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study
Sundar R, Bandla A, Tan S, Liao L, Kumarakulasinghe N, Jeyasekharan A, Ow S, Ho J, Tan D, Lim J, Vijayan J, Therimadasamy A, Hairom Z, Ang E, Ang S, Thakor N, Lee S, Wilder-Smith E. Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study. Frontiers In Oncology 2017, 6: 274. PMID: 28119855, PMCID: PMC5222823, DOI: 10.3389/fonc.2016.00274.Peer-Reviewed Original ResearchNerve conduction studiesBreast cancer patientsPeripheral neuropathyPaclitaxel infusionLimb hypothermiaPreventing paclitaxel-induced peripheral neuropathyCancer patientsPaclitaxel-induced peripheral neuropathyHistory of diabetes mellitusDose-limiting toxicityCompound muscle action potentialCool limbsMuscle action potentialWeekly paclitaxelSensory velocityDiabetes mellitusGrade 2Contralateral limbAction potentialsPaclitaxelPilot trialPatientsControl limbsHypothermiaTolerance to hypothermia
2016
Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy
Sundar R, Jeyasekharan A, Pang B, Soong R, Kumarakulasinghe N, Ow S, Ho J, Lim J, Tan D, Wilder-Smith E, Bandla A, Tan S, Asuncion B, Fazreen Z, Hoppe M, Putti T, Poh L, Goh B, Lee S. Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy. PLOS ONE 2016, 11: e0164319. PMID: 27716814, PMCID: PMC5055363, DOI: 10.1371/journal.pone.0164319.Peer-Reviewed Original ResearchConceptsPaclitaxel-induced neuropathySevere neuropathyReceiver operating characteristicNerve tissueDose-limiting toxicityEarly breast cancerSensory peripheral neuropathyArea under the curveBreast cancer patientsIntensity of stainingWeekly paclitaxelSurgical resectionCharcot-Marie-ToothLimiting toxicitiesPredictive biomarkersNerve biopsyPeripheral neuropathyBreast cancerBiomarker strategiesCancer patientsNDRG1 expressionNeuropathyExpression scorePatientsPaclitaxel