2024
Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes
Sundar R, Chia D, Zhao J, Lee A, Kim G, Tan H, Pang A, Shabbir A, Willaert W, Ma H, Huang K, Hagihara T, Tan A, Ong C, Wong J, Seo C, Walsh R, Chan G, Cheo S, Soh C, Callebout E, Geboes K, Ng M, Lum J, Leow W, Selvarajan S, Hoorens A, Ang W, Pang H, Tan P, Yong W, Chia C, Ceelen W, So J. Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes. ESMO Open 2024, 9: 103681. PMID: 39288528, PMCID: PMC11421236, DOI: 10.1016/j.esmoop.2024.103681.Peer-Reviewed Original ResearchConceptsGastric cancer peritoneal metastasisPeritoneal cancer indexNivolumab combinationPeritoneal metastasisPeritoneal tumorsNaive CD8+ T cellsCD8+ central memoryEnhanced T cell infiltrationTreatment-related adverse eventsCD8+ T cellsGrade 4 vomitingRegression grade 1First-in-human trialImmune checkpoint inhibitionMemory CD4+T cell infiltrationImmunogenic cell deathSystemic immunotherapyCheckpoint inhibitionSystemic therapyCancer indexCD4+Intraperitoneal treatmentT cellsAdverse events229TiP A phase II trial of a neural network-based treatment decision support tool in patients (pts) with refractory solid organ malignancies
Walsh R, Jayagopal A, Tan T, Pitt J, Sundar R, Lee S, Goh B, Rajan V, Tan D, Jeyasekharan A. 229TiP A phase II trial of a neural network-based treatment decision support tool in patients (pts) with refractory solid organ malignancies. Annals Of Oncology 2024, 35: s307-s308. DOI: 10.1016/j.annonc.2024.08.2233.Peer-Reviewed Original Research1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial
Sachdeva M, Tay R, KIM Y, Kim H, Cheong J, Grabsch H, Sundar R. 1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial. Annals Of Oncology 2024, 35: s885. DOI: 10.1016/j.annonc.2024.08.1484.Peer-Reviewed Original ResearchEORTC stomach cancer PD-L1 biomarker European initiative: the ASPIRE study protocol
Petrillo A, Oudijk L, Sundar R, Daumer C, Casas J, D’Haese D, Mauer M, van Grieken N, Smyth E, Moehler M. EORTC stomach cancer PD-L1 biomarker European initiative: the ASPIRE study protocol. ESMO Gastrointestinal Oncology 2024, 5: 100071. DOI: 10.1016/j.esmogo.2024.100071.Peer-Reviewed Original ResearchPersonalized dose selection for the first Waldenström macroglobulinemia patient on the PRECISE CURATE.AI trial
Blasiak A, Tan L, Chong L, Tadeo X, Truong A, Senthil Kumar K, Sapanel Y, Poon M, Sundar R, de Mel S, Ho D. Personalized dose selection for the first Waldenström macroglobulinemia patient on the PRECISE CURATE.AI trial. Npj Digital Medicine 2024, 7: 223. PMID: 39191913, PMCID: PMC11350179, DOI: 10.1038/s41746-024-01195-5.Peer-Reviewed Original ResearchArtificial intelligenceClinical decision support systemsDecision support systemIntegration of AIAI-enabled toolsWaldenstrom's macroglobulinemiaBruton tyrosine kinase inhibitor ibrutinibRare diseaseEnhance usersWaldenstrom's macroglobulinemia patientsKinase inhibitor ibrutinibSupport systemSecondary outcome measuresDiagnosed WMDigital health solutionsWM patientsInhibitor ibrutinibMacroglobulinemia patientsDosing recommendationsUsersManagement of rare diseasesClinical efficacyDevelopment of digital technologiesDose selectionPersonalized therapySpatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases
Zhao J, Ong C, Srivatsava S, Ann Chia D, Ma H, Huang K, Sheng T, Ramnarayanan K, Ong X, Tay S, Hagihara T, Keng Tan A, Ching Teo M, Tan Q, Ng G, Tan J, Hsien Ng M, Gwee Y, Walsh R, Law J, Shabbir A, Kim G, Tay Y, Her Z, Leoncini G, The B, Hong J, Kiat Tay R, Teo C, Dings M, Bijlsma M, Yew Lum J, Mathur S, Pietrantonio F, Blum S, van Laarhoven H, Klempner S, Yong W, So J, Chen Q, Tan P, Sundar R. Spatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases. Gastroenterology 2024 PMID: 39147169, DOI: 10.1053/j.gastro.2024.08.007.Peer-Reviewed Original ResearchPeritoneal metastasisTumor microenvironmentPrimary tumorTranscoelomic metastasisGastric cancerExpression of therapeutic targetsAssociated with poor prognosisGastric cancer peritoneal metastasisAssociated with increased riskHumanized mouse modelTherapeutic targetComprehensive multi-omics analysisTumor microenvironment signaturesTumor microenvironment alterationsDigital spatial profilingInvestigate molecular alterationsWhole-exome sequencingMatched normal tissuesStromal infiltrationComprehensive molecular characterizationLiver metastasesImmune compositionFGFR2b expressionImprove patient outcomesPredictive markerA 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 modelsCHAPTER-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 survivalImmunogenicity of Abdala COVID-19 vaccine in Vietnamese people after primary and booster vaccinations: a prospective observational study in Vietnam
Thanh T, Tu N, Nguyet L, Thuy C, Thuan N, Ny N, Nhu L, Thanh L, Hong N, Anh N, Truong N, Van Vinh Chau N, Yen L, Van E P, Thuong N, Van Truc N, Trung P, Yap W, Pandey R, Yee S, Weng R, Mongkolsapaya J, Dejnirattisai W, Hamers R, Chantratita N, Screaton G, Dunachie S, Jones E, Stuart D, Dung N, Thwaites G, Wang L, Tan C, Van Tan L, Wang L, Cruz K, Yee S, Lu H, Ruifen W, Pandey R, Young B, Sundar R, Soebandrio A, Sawitri A, Sutarsa I, Chan Y, Jantarabenjakul W, Chan N, Tan C, Van Tan L, Anh N, Hong N, Truc T, Ny N, Han D, Thanh L, Nguyet L, Thuy C, Nhu L, Thanh T, Yen L, Hang V, Kieu P, Hoang V, Thao N, Chambers M, Thanh V, Hoang T, van Doorn H, Tung T, Thwaites C, Thwaites G, Wang L, Lim B, Hamers R, Shankar A, Suwarti S, Tayipto Y, Simarmata E, Dien R, Mongkolsapaya J, Dejnirattisai W, Chantima W, Chantratita N, Poolchanuan P, Tiacharoen V, Dulsuk A, Iamsirithaworn S, Day N, Cheah P, Poomchaichote T, Boonthaworn K, Screaton G, Dijokaite-Guraliuc A, Das R, Liu C, Supasa P, Selvaraj M, Dunachie S, Klenerman P, Jones E, Stuart D, Kronsteiner-Dobramysl B, Zewdie M, Abraham P, Hill J, Ngoc N, Grifoni A, Sette A, Yap W, Tan C, Van Tan L. Immunogenicity of Abdala COVID-19 vaccine in Vietnamese people after primary and booster vaccinations: a prospective observational study in Vietnam. International Journal Of Infectious Diseases 2024, 147: 107173. PMID: 39094762, DOI: 10.1016/j.ijid.2024.107173.Peer-Reviewed Original ResearchSARS-CoV-2 variantsSARS-CoV-2Neutralizing antibodiesBooster doseCOVID-19 vaccineCross-neutralizationAntibody responseMeasured anti-nucleocapsidVietnamese healthcare workersBooster vaccinationSARS-CoV-1Ancestral SARS-CoV-2Anti-spike antibodiesProspective observational studyCross-neutralizing activityProtein subunit vaccinesEnhanced antibody responseNeutralizing antibody titersMRNA BNT162b2ChAdOx1 vaccineAnti-spikeAnti-nucleocapsidPrimary vaccinationCollected blood samplesObservational studyProofreading the way: immune checkpoint inhibitors in polymerase ε/polymerase δ (POLE/POLD1)-altered colorectal cancer
Cecchini M, Sundar R. Proofreading the way: immune checkpoint inhibitors in polymerase ε/polymerase δ (POLE/POLD1)-altered colorectal cancer. Annals Of Oncology 2024, 35: 582-584. PMID: 38910015, DOI: 10.1016/j.annonc.2024.04.006.Peer-Reviewed Original ResearchState-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care.
Balmaceda N, Petrillo A, Krishnan M, Zhao J, Kim S, Klute K, Sundar R. State-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care. American Society Of Clinical Oncology Educational Book 2024, 44: e431060. PMID: 38771996, DOI: 10.1200/edbk_431060.Peer-Reviewed Original ResearchConceptsGastroesophageal cancerIntegration of immune checkpoint inhibitorsChimeric antigen receptor T cellsImmune checkpoint inhibitorsMetastatic gastroesophageal cancerPD-1 inhibitorsAdoptive cell therapyImmunotherapy-based approachesResectable gastroesophageal cancerAntibody-drug conjugatesCheckpoint inhibitorsPD-1Perioperative chemotherapyTargeted therapyT cellsTreatment paradigmFGFR2 inhibitorsCell therapyClinical challengeBispecific antibodiesImprove outcomesCancer treatmentReduced toxicityTherapyInhibitorsA 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-CD137Molecular profiling of metastatic breast cancer and target-based therapeutic matching in an Asian tertiary phase I oncology unit
Walsh R, Ong R, Cheo S, Low P, Jayagopal A, Lee M, Ngoi N, Ow S, Wong A, Lim S, Lim Y, Heong V, Sundar R, Soo R, Chee C, Yong W, Goh B, Lee S, Tan D, Lim J. Molecular profiling of metastatic breast cancer and target-based therapeutic matching in an Asian tertiary phase I oncology unit. Frontiers In Oncology 2024, 14: 1342346. PMID: 38812774, PMCID: PMC11133600, DOI: 10.3389/fonc.2024.1342346.Peer-Reviewed Original ResearchProlonged median progression-free survivalTumor mutational burdenObjective response rateMetastatic breast cancerHazard ratioNext-generation sequencingPhase I unitMedian OSMolecular profilingOverall survivalAssociated with prolonged median PFSBreast cancerMedian progression-free survivalTreatment outcomesTrials of targeted therapiesProgression-free survivalData cut-offBroad-panel next-generation sequencingTumor molecular profilingTreatment eventsFoundationOne CDxMBC patientsMutational burdenAssociated with improvementsTertiary centrePushing the Frontiers of Cancer Research: Highlights from the Frontiers in Cancer Science Conference 2023.
Lee Y, Chen L, Chew V, Chow E, Deng L, Hunziker W, Lee A, Leong G, Ngeow J, Pervaiz S, Sabapathy K, Skanderup A, Sundar R, Tay Y, Virshup D, Wong S, Tergaonkar V, Tam W. Pushing the Frontiers of Cancer Research: Highlights from the Frontiers in Cancer Science Conference 2023. Cancer Research 2024, 84: 1195-1198. PMID: 38616656, DOI: 10.1158/0008-5472.can-24-0721.Peer-Reviewed Original ResearchAbstract P28: Comprehensive Molecular Phenotyping of ARID1A -deficient Gastric Cancer Reveals Pervasive Epigenomic Reprogramming and Therapeutic Opportunities
Xu C, Huang K, Law J, Chua J, Sheng T, Flores N, Pizzi M, Okabe A, Tan A, Zhu F, Kumar V, Lu X, Benitez A, Lian B, Ma H, Ho S, Ramnarayanan K, Anene-Nzelu C, Razavi-Mohseni M, Ghani S, Tay S, Ong X, Lee M, Guo Y, Ashktorab H, Smoot D, Li S, Skanderup A, Beer M, Foo R, Wong J, Sanghvi K, Yong W, Sundar R, Kaneda A, Prabhakar S, Mazur P, Ajani J, Yeoh K, So J, Tan P. Abstract P28: Comprehensive Molecular Phenotyping of ARID1A -deficient Gastric Cancer Reveals Pervasive Epigenomic Reprogramming and Therapeutic Opportunities. Cancer Research 2024, 84: p28-p28. DOI: 10.1158/1538-7445.fcs2023-p28.Peer-Reviewed Original ResearchGastric cancerMolecular subtypesARID1A lossPro-inflammatory tumor microenvironmentTherapeutic opportunitiesARID1A inactivationTumor microenvironmental changesEpigenomic reprogrammingMutational signaturesPromoter activityGastric cell linesARID1A depletionTumor-intrinsicTumor inflammationTumor microenvironmentSingle-cell transcriptome profilingMutated driver genesTherapeutic vulnerabilitiesGC molecular subtypesNFkB inhibitorARID1ATherapeutic strategiesPharmacological inhibitionGC patientsSingapore cohortAbstract P37: Establishment of Gastric Organoids Biobank and Its Usage
Hagihara T, Huang K, Sundar R, Uchihara T, Ng C, Tay S, Tan A, So J, Tan P. Abstract P37: Establishment of Gastric Organoids Biobank and Its Usage. Cancer Research 2024, 84: p37-p37. DOI: 10.1158/1538-7445.fcs2023-p37.Peer-Reviewed Original ResearchAbstract 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 escalationAbstract 2759: Transcriptional intra-tumoral heterogeneity of putative therapeutic targets in colorectal cancer peritoneal metastases
Zhao J, Ong J, Chia D, Teo M, Tan Q, Ng G, Tan J, Ma H, Ong X, Tay S, Tan P, Sundar R. Abstract 2759: Transcriptional intra-tumoral heterogeneity of putative therapeutic targets in colorectal cancer peritoneal metastases. Cancer Research 2024, 84: 2759-2759. DOI: 10.1158/1538-7445.am2024-2759.Peer-Reviewed Original ResearchColorectal cancer peritoneal metastasesCRC PMPeritoneal metastasisColorectal cancerIntra-tumor heterogeneitySystemic regimensTherapeutic targetAmerican Association for Cancer Research annual meetingsPrognosis of peritoneal metastasisResistant to systemic chemotherapyPlasma-peritoneal barrierOncological surgical resectionColorectal cancer patientsSystemic chemotherapySurgical resectionPalliative surgerySystemic therapyAntineoplastic therapyPotential therapeutic targetExploratory laparotomyTranscoelomic metastasisPoor prognosisFFPE tissue samplesSynchronous PMPoor responseAbstract 1497: Humanized mouse model unveils niche conditioning in gastric cancer peritoneal metastasis
Zhao J, Chia D, Her Z, Ma H, Ong X, Tay S, So J, Chen Q, Tan P, Sundar R. Abstract 1497: Humanized mouse model unveils niche conditioning in gastric cancer peritoneal metastasis. Cancer Research 2024, 84: 1497-1497. DOI: 10.1158/1538-7445.am2024-1497.Peer-Reviewed Original ResearchHumanized mouse modelPeritoneal metastasisGastric cancer peritoneal metastasisPrimary tumorAdjacent peritoneumMouse modelTranscoelomic metastasisHost immune systemEpithelial mesenchymal transitionOrthotopic modelAmerican Association for Cancer Research annual meetingsGastric cancerNovel humanized mouse modelNSG modelImmune systemExpression of M2 macrophagesFunctional human cellsPeritoneal disseminationT-regsOrthotopic inoculationDendritic cellsNOD-SCIDImmune infiltrationPeritoneal samplesNormal peritoneumCharting the path forward in Southeast Asia: Learning from the COVID-19 vaccination challenges in six ASEAN countries
Fu J, Pukhari M, Dela Cruz K, Soebandrio A, Tan L, Jantarabenjakul W, Sawitri A, Chantasrisawad N, Yee S, Weng R, Sundar R, Tan C, Wang L, Sam I, Young B, Sutarsa I, Chan Y, Putcharoen O, Wacharapluesadee S, Syed Omar S, Rajasuriar R, Kukreja A, Basri S, Kamarulzaman A, Tan C, Said A, Su’ut L, Tu N, Thuy C, Nguyet L, Thanh L, Ny N, Hong N, Nhu L, Thanh T, Truong N, Ho Y, Pandey R, Diong S, Libau E, Ongko J, Lim J, Abdullah R, Yeo H, Chin Y, Jin J, Lim B, Zhu F, Chee Y, Lumandas M, Dizon T, Demetria C, Biocarles M, Inobaya M, Sornillo J, Morin J, Digman A, Roxas C, Jiz M, Pinatih K, Yuliyatni P, Manuaba I, Wisnawa I, Kusmawati A, Rissa Cempaka P. Charting the path forward in Southeast Asia: Learning from the COVID-19 vaccination challenges in six ASEAN countries. Journal Of Global Health 2024, 14: 03016. PMCID: PMC10940960, DOI: 10.7189/jogh.14.03016.Peer-Reviewed Original Research