2025
The MATRiX trial: A multicenter, randomized, phase II study of ATR inhibition (via tuvusertib) with or without avelumab in patients with advanced anti-PD-(L)1–refractory Merkel cell carcinoma.
Bhakuni R, Hall E, Ansstas G, Bhatia S, Brohl A, Burgess M, Dimitrova M, Gao L, Ishizuka J, Lipson E, Lutzky J, Silk A, Yun J, Brownell I, Murray J, Mowery Y, Gooley T, Gore S, Topalian S, Nghiem P. The MATRiX trial: A multicenter, randomized, phase II study of ATR inhibition (via tuvusertib) with or without avelumab in patients with advanced anti-PD-(L)1–refractory Merkel cell carcinoma. Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.tps9598.Peer-Reviewed Original ResearchMerkel cell carcinomaProgression-free survivalCell carcinomaProgressive diseaseATR inhibitionDay 1PD-1 pathway inhibitorsRare neuroendocrine skin cancerRecommended phase II doseAnti-tumor immune responseTreatment-emergent adverse eventsKi-67 proliferative indexPD-(L)1 blockadePhase II doseResponse Evaluation CriteriaPhase II studySolid tumor immunotherapyInduce tumor regressionNeuroendocrine skin cancerPhase I trialLog-rank testMerkel cell polyomavirusHigh response rateCell cycle checkpoint regulationII doseSafety and Antitumor Activity of a Novel aCD25 Treg Depleter RG6292 as a Single Agent and in Combination with Atezolizumab in Patients with Solid Tumors
Gambardella V, Ong M, Rodriguez-Ruiz M, Machiels J, Sanmamed M, Galvao V, Spreafico A, Renouf D, Luen S, Galot R, de Spéville B, Calvo E, Naing A, Curdt S, Kolben T, Rossmann E, Tanos T, Smart K, Amann M, Xie Y, Xu L, Alcaide E, Städler N, Justies N, Boetsch C, Karanikas V, Schnetzler G, Rohrberg K. Safety and Antitumor Activity of a Novel aCD25 Treg Depleter RG6292 as a Single Agent and in Combination with Atezolizumab in Patients with Solid Tumors. Cancer Research Communications 2025, 5: 422-432. PMID: 39983024, PMCID: PMC11891644, DOI: 10.1158/2767-9764.crc-24-0638.Peer-Reviewed Original ResearchConceptsRecommended phase II dosePhase II doseMaximum tolerated dosePhase I studyTreg depletionSolid tumorsII doseTolerated doseResistance to cancer immunotherapyRegulatory T-cell depletionImmunosuppressive regulatory T cellsEffector T cell functionAdvanced solid tumorsT-cell depletionRegulatory T cellsAnti-CD25 antibodyFrequent adverse eventsT cell functionDose-dependent depletionIL-2 signalingAtezolizumab combinationDeplete TregsTreg reductionDose escalationPeripheral Tregs
2023
Determination and Confirmation of Recommended Ph2 Dose of Amivantamab in Epidermal Growth Factor Receptor Exon 20 Insertion Non‐Small Cell Lung Cancer
Haddish‐Berhane N, Su Y, Russu A, Thayu M, Knoblauch R, Mehta J, Xie J, Gibbs E, Sun Y, Zhou H. Determination and Confirmation of Recommended Ph2 Dose of Amivantamab in Epidermal Growth Factor Receptor Exon 20 Insertion Non‐Small Cell Lung Cancer. Clinical Pharmacology & Therapeutics 2023, 115: 468-477. PMID: 37776107, DOI: 10.1002/cpt.3064.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerAdverse events of clinical interestEpidermal growth factor receptor-exonPopPK modelRecommended phase II dosePrimary efficacy end pointEGFR exon 20 insertionsPhase II doseExon 20 insertionsEfficacy end pointCovariates of clearanceVolume of distributionE-R relationshipSerum concentration dataEGFR ex20insII doseExposure-response analysesPlatinum chemotherapyExposure-responseEfficacy analysisPK variabilityPopulation PKAmivantamab
2022
Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma
Girgis S, Lin S, Pillarisetti K, Banerjee A, Stephenson T, Ma X, Shetty S, Yang T, Hilder B, Jiao Q, Hanna B, Adams H, Sun Y, Sharma A, Smit J, Infante J, Goldberg J, Elsayed Y. Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. Targeted Oncology 2022, 17: 433-439. PMID: 35749004, PMCID: PMC9345835, DOI: 10.1007/s11523-022-00893-y.Peer-Reviewed Original ResearchConceptsPhase I studyTherapeutic dose rangeSubcutaneous doseMultiple myelomaTherapeutic rangeActive dosesRecommended phase II doseDose rangeT cell-mediated cytotoxicityLow-dose cohortPhase II doseDose-escalation studyRelapsed/Refractory Multiple MyelomaWeekly subcutaneous dosesCD3 bispecific antibodyFirst-in-humanMultiple myeloma cellsII doseResultsThe doseEscalation studyIntravenous doseBone marrowPreclinical studiesB cellsClinical dataPhase 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
2008
A Phase 1 Dose-Escalation Study of Irinotecan in Combination with 17-Allylamino-17-Demethoxygeldanamycin in Patients with Solid Tumors
Tse A, Klimstra D, Gonen M, Shah M, Sheikh T, Sikorski R, Carvajal R, Mui J, Tipian C, O'Reilly E, Chung K, Maki R, Lefkowitz R, Brown K, Manova-Todorova K, Wu N, Egorin M, Kelsen D, Schwartz G. A Phase 1 Dose-Escalation Study of Irinotecan in Combination with 17-Allylamino-17-Demethoxygeldanamycin in Patients with Solid Tumors. Clinical Cancer Research 2008, 14: 6704-6711. PMID: 18927314, PMCID: PMC3996559, DOI: 10.1158/1078-0432.ccr-08-1006.Peer-Reviewed Original ResearchConceptsMaximum tolerated doseSolid tumorsG(2)-M cell cycle checkpointPhase I study of irinotecanPhase 1 dose-escalation studyRecommended phase II doseDose level 4P53-wildtype tumorsTumor p53 statusCombination of irinotecanDose-escalation phaseDose-limiting toxicityPhase II dosePhase I studyHSP90 inhibitor 17AAGP53 mutant tumorsPharmacokinetics of irinotecanTumor biopsy samplesCoadministration of irinotecanCheckpoint kinase 1II doseStable diseaseTumor shrinkageTolerated dosePulmonary embolism
2005
A Phase I Study of Estramustine, Weekly Docetaxel, and Carboplatin Chemotherapy in Patients with Hormone-Refractory Prostate Cancer
Oh W, Hagmann E, Manola J, George D, Gilligan T, Jacobson J, Smith M, Kaufman D, Kantoff P. A Phase I Study of Estramustine, Weekly Docetaxel, and Carboplatin Chemotherapy in Patients with Hormone-Refractory Prostate Cancer. Clinical Cancer Research 2005, 11: 284-289. PMID: 15671557, DOI: 10.1158/1078-0432.284.11.1.Peer-Reviewed Original ResearchConceptsHormone-refractory prostate cancerProstate-specific antigen declineProstate-specific antigenRecommended phase II doseMaximal tolerated doseTolerated doseProstate cancerRecommended phase II dose of docetaxelDose levelsMedian prostate-specific antigenDocetaxel dose escalationDose of docetaxelPhase II doseDose-limiting toxicityEfficacy of docetaxelPhase I studyHighest dose levelDelayed thrombocytopeniaII doseSignificant myelosuppressionDose escalationMedian survivalPartial responseCarboplatin chemotherapyMedian age
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