2022
A phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies
Ho J, Heong V, Yong W, Soo R, Chee C, Wong A, Sundar R, Thian Y, Gopinathan A, Pang M, Koe P, Jeraj S, Soe P, Soe M, Tang T, Ng M, Tai D, Tan T, Xu H, Chang H, Landesman Y, Shah J, Shacham S, Lee S, Tan D, Goh B, Tan D. A phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies. Therapeutic Advances In Medical Oncology 2022, 14: 17588359221087555. PMID: 35432603, PMCID: PMC9008867, DOI: 10.1177/17588359221087555.Peer-Reviewed Original ResearchPhase 1 studyAsian patientsMetastatic malignancyMedian t<sub>max</sub> wasGrade 3 adverse eventsNCI Common Terminology CriteriaRecommended phase 2 doseAsian patient cohortContinuous dosing regimensGrade 3 fatiguePhase 2 doseThymic carcinoma patientsDose-escalation designCommon Terminology CriteriaInhibitor of nuclear exportCytoplasmic localization of p27Dose expansionComplete responseHodgkin lymphomaExpansion cohortLymphoma patientsPartial responseDrug holidayEscalation designPharmacodynamic assessments
2020
Clinical efficacy and molecular effects of lenvatinib (Len) and letrozole (Let) in hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Lim J, Wong A, Ow S, Ngoi N, Ang Y, Chan G, Eng L, Chong W, Choo J, Lee M, Tan H, Jan Y, Tan K, Sundar R, Tan D, Soo R, Chee C, Yong W, Goh B, Lee S. Clinical efficacy and molecular effects of lenvatinib (Len) and letrozole (Let) in hormone receptor-positive (HR+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2020, 38: 1019-1019. DOI: 10.1200/jco.2020.38.15_suppl.1019.Peer-Reviewed Original ResearchDisease control rateObjective response rateMetastatic breast cancerEffect of lenvatinibDose escalationEndocrine therapyEfficacy dataRecommended phase 2 doseAll-grade toxicitiesPhase 2 doseDose-escalation phaseHormone receptor-positiveDuration of responsePhase Ib/II studyTumor molecular profilingSerial tumor biopsiesAnti-tumor activityMolecular effectsMedian DoRPrior CTPALB2 mutationsProgression-freeExpansion cohortMBC patientsReceptor-positive
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
2017
TAX-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 PO