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 models
2022
Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer.
Lim J, Wong A, Ow S, Ngoi N, Chan G, Ang Y, Chong W, Lim S, Lim Y, Lee M, Choo J, Tan H, Yong W, Soo R, Tan D, Chee C, Sundar R, Yadav K, Jain S, Wang L, Tai B, Goh B, Lee S. Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer. Clinical Cancer Research 2022, 28: 2248-2256. PMID: 35363275, DOI: 10.1158/1078-0432.ccr-21-4179.Peer-Reviewed Original ResearchConceptsBreast cancerDose expansionEstrogen receptorHormone receptor-positive breast cancerPhase II dose expansionRecommended phase II doseReceptor-positive breast cancerCDK4/6 inhibitor therapyDose-expansion studyPaired tumor biopsiesPhase Ib/II trialPhase II doseVascular normalization indexTreated with lenvatinibDose of lenvatinibER+/HER2- breast cancerMetastatic breast cancerPreliminary antitumor activityEstrogen-responsive genesLenvatinib combinationII doseMetastatic settingInhibitor therapyMultikinase inhibitorTumor biopsies
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 levels
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 trial
2016
Phase Ib/II randomized, open-label study of doxorubicin and cyclophosphamide with or without low-dose, short-course sunitinib in the pre-operative treatment of breast cancer
Wong A, Sundar R, Wang T, Ng T, Zhang B, Tan S, Soh T, Pang A, Tan C, Ow S, Wang L, Mogro J, Ho J, Jeyasekharan A, Huang Y, Thng C, Chan C, Hartman M, Iau P, Buhari S, Goh B, Lee S. Phase Ib/II randomized, open-label study of doxorubicin and cyclophosphamide with or without low-dose, short-course sunitinib in the pre-operative treatment of breast cancer. Oncotarget 2016, 7: 64089-64099. PMID: 27577069, PMCID: PMC5325427, DOI: 10.18632/oncotarget.11596.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnthracyclinesAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsContrast MediaCyclophosphamideDisease-Free SurvivalDoxorubicinDrug Administration ScheduleFemaleHumansImmunohistochemistryIndolesMagnetic Resonance ImagingMiddle AgedNeoadjuvant TherapyPreoperative PeriodPyrrolesSunitinibTreatment OutcomeConceptsPathological complete responseVascular normalization indexChemotherapy dose delaysLow-doseDose delaysDCE-MRIPhase IbDecreased lymphatic vessel densityIntra-tumoral drug deliveryPathologic complete response rateRecommended phase II dosePhase II doseDose of sunitinibTreatment of breast cancerDCE-MRI parametersPre-operative treatmentAnthracycline-based chemotherapyOpen-label studyRandomized to chemotherapyTumor vessel normalizationLymphatic vessel densityEnhance chemotherapy efficacyBreast cancer patientsFunctional imaging biomarkersPharmacodynamic evidence