2023
A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors
Garralda E, Schram A, Bedard P, Schwartz G, Yuen E, McNeely S, Ribeiro S, Cunningham J, Wang Y, Urunuela A, Xu X, LoRusso P. A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors. The Oncologist 2023, 29: e131-e140. PMID: 37531083, PMCID: PMC10769797, DOI: 10.1093/oncolo/oyad215.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsAdvanced solid tumorsCyclin-dependent kinase 7Adverse eventsSolid tumorsPhase I dose-escalation studyI dose-escalation studyLimited clinical activityGastrointestinal adverse eventsDose-escalation studyDose-limiting toxicityPhase I trialBest overall responsePeak-trough fluctuationKinase 7Common toxicitiesStable diseaseAbdominal painPrimary endpointSecondary endpointsAdult patientsPartial responseComplete responseI trialMedian timeNCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors
Cecchini M, Walther Z, Wei W, Hafez N, Pilat M, Boerner S, Durecki D, Eder J, Schalper K, Chen A, LoRusso P. NCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors. Cancer Research Communications 2023, 3: 1113-1117. PMID: 37377610, PMCID: PMC10292219, DOI: 10.1158/2767-9764.crc-22-0485.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityHomologous recombination deficiencyPARP inhibitorsStable diseaseWeekly irinotecanObjective responseDay 1Day 3Solid tumorsPhase I dose-escalation studyTwice daily days 1I dose-escalation studyPhase I clinical trialDaily days 1Dose level 1Doses of veliparibGrade 3 neutropeniaMultiple-dose schedulesProgression-free survivalAdvanced solid tumorsDose-escalation studyEvaluable patientsNonoverlapping toxicitiesDose scheduleSystemic treatment
2021
A phase I dose-escalation study of the MDM2-p53 antagonist BI 907828 in patients (pts) with advanced solid tumors.
LoRusso P, Gounder M, Patel M, Yamamoto N, Bauer T, Laurie S, Grempler R, Davenport T, Geng J, Rohrbacher M, Lahmar M. A phase I dose-escalation study of the MDM2-p53 antagonist BI 907828 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2021, 39: 3016-3016. DOI: 10.1200/jco.2021.39.15_suppl.3016.Peer-Reviewed Original ResearchDose-limiting toxicityAdvanced solid tumorsArm AAdverse eventsArm BSolid tumorsDay 1Phase I dose-escalation studyExperienced dose-limiting toxicityNon-hematologic adverse eventsTreatment-related adverse eventsI dose-escalation studyAntitumor activityBiomarkers GDF-15Dose-escalation partGrade 3 nauseaManageable safety profileMDM2-p53 antagonistsPreliminary PK dataDose-escalation studyPatient-derived xenograftsClearance/FCycle 1Favorable PK propertiesLogistic regression models
2011
Phase I dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy
Garrett C, Siu L, El-Khoueiry A, Buter J, Rocha-Lima C, Marshall J, LoRusso P, Major P, Chemidlin J, Mokliatchouk O, Velasquez L, Hayes W, Feltquate D, Syed S, Ford S, Kollia G, Galbraith S, Nuyten D. Phase I dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy. British Journal Of Cancer 2011, 105: 44-52. PMID: 21629245, PMCID: PMC3137402, DOI: 10.1038/bjc.2011.182.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlanineAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCetuximabDrug Therapy, CombinationFemaleGastrointestinal NeoplasmsHumansMaleMiddle AgedNeoplasm Recurrence, LocalSalvage TherapySurvival RateTissue DistributionTreatment OutcomeTriazinesVascular Endothelial Growth Factor Receptor-2ConceptsAdvanced gastrointestinal malignanciesGastrointestinal malignanciesPhase I dose-escalation studyAdvanced metastatic colorectal cancerCommon treatment-related toxicitiesMedian progression-free survivalI dose-escalation studyRadiographic partial responseMetastatic colorectal cancerTreatment-related toxicityAcceptable toxicity profileDose-escalation studyPhase III studyProgression-free survivalOverall response rateK-ras mutationsAcneiform dermatitisPrior therapyAdverse eventsIII studyMedian durationMucosal inflammationPartial responseCombination chemotherapyColorectal cancerPhase I dose-escalation study of AZD7762 in combination with gemcitabine (gem) in patients (pts) with advanced solid tumors.
Sausville E, LoRusso P, Carducci M, Barker P, Agbo F, Oakes P, Senderowicz A. Phase I dose-escalation study of AZD7762 in combination with gemcitabine (gem) in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2011, 29: 3058-3058. DOI: 10.1200/jco.2011.29.15_suppl.3058.Peer-Reviewed Original ResearchPhase I dose-escalation studyI dose-escalation studyAdvanced solid tumorsDose-escalation studySolid tumorsA phase I dose-escalation study of the novel gamma secretase inhibitor PF-03084014 in patients (pts) with advanced solid tumors.
Messersmith W, LoRusso P, Cleary J, Dasari A, Zhang X, Shaik M, Courtney R, Randolph S, Shapiro G. A phase I dose-escalation study of the novel gamma secretase inhibitor PF-03084014 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2011, 29: 3100-3100. DOI: 10.1200/jco.2011.29.15_suppl.3100.Peer-Reviewed Original ResearchA phase I dose-escalation study of the Hsp90 inhibitor ganetespib (STA-9090) administered twice weekly in patients with solid tumors: Updated report.
Cho D, Heath E, Cleary J, Kwak E, Gandhi L, Lawrence D, Zack C, Teofilovici F, Bradley R, Karol M, Shapiro G, LoRusso P. A phase I dose-escalation study of the Hsp90 inhibitor ganetespib (STA-9090) administered twice weekly in patients with solid tumors: Updated report. Journal Of Clinical Oncology 2011, 29: 3051-3051. DOI: 10.1200/jco.2011.29.15_suppl.3051.Peer-Reviewed Original ResearchPhase I dose-escalation studyI dose-escalation studyDose-escalation studyHSP90 inhibitor ganetespibSolid tumorsA phase I dose-escalation study to evaluate GDC-0941, a pan-PI3K inhibitor, administered QD or BID in patients with advanced or metastatic solid tumors.
Von Hoff D, LoRusso P, Demetri G, Weiss G, Shapiro G, Ramanathan R, Ware J, Raja R, Jin J, Levy G, Mazina K, Wagner A. A phase I dose-escalation study to evaluate GDC-0941, a pan-PI3K inhibitor, administered QD or BID in patients with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2011, 29: 3052-3052. DOI: 10.1200/jco.2011.29.15_suppl.3052.Peer-Reviewed Original ResearchPhase I dose-escalation study of ALN-VSP02, a novel RNAi therapeutic for solid tumors with liver involvement.
Cervantes A, Alsina M, Tabernero J, Infante J, LoRusso P, Shapiro G, Paz-Ares L, Falzone R, Hill J, Cehelsky J, White A, Toudjarska I, Bumcrot D, Meyers R, Hinkle G, Svrzikapa N, Sah D, Vaishnaw A, Gollob J, Burris H. Phase I dose-escalation study of ALN-VSP02, a novel RNAi therapeutic for solid tumors with liver involvement. Journal Of Clinical Oncology 2011, 29: 3025-3025. DOI: 10.1200/jco.2011.29.15_suppl.3025.Peer-Reviewed Original ResearchPhase I dose-escalation studyI dose-escalation studyDose-escalation studyLiver involvementSolid tumorsTumors
2010
A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765 (SAR245409), a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced malignancies.
Brana I, LoRusso P, Baselga J, Heath E, Patnaik A, Gendreau S, Laird A, Papadopoulos K. A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765 (SAR245409), a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced malignancies. Journal Of Clinical Oncology 2010, 28: 3030-3030. DOI: 10.1200/jco.2010.28.15_suppl.3030.Peer-Reviewed Original ResearchA phase I dose-escalation study of the Hsp90 inhibitor STA-9090 administered twice weekly in patients with solid tumors.
Cleary J, Heath E, Kwak E, Dezube B, Gandhi L, Zack C, Bradley R, Vukovic V, Shapiro G, LoRusso P. A phase I dose-escalation study of the Hsp90 inhibitor STA-9090 administered twice weekly in patients with solid tumors. Journal Of Clinical Oncology 2010, 28: 3083-3083. DOI: 10.1200/jco.2010.28.15_suppl.3083.Peer-Reviewed Original Research
2009
A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765, a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced solid tumors
LoRusso P, Markman B, Tabernero J, Shazer R, Nguyen L, Heath E, Patnaik A, Papadopoulos K. A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765, a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2009, 27: 3502-3502. DOI: 10.1200/jco.2009.27.15_suppl.3502.Peer-Reviewed Original ResearchAdverse eventsPhase I dose-escalation studyI dose-escalation studyDurable stable diseaseElevated hepatic transaminasesFood-induced increaseElevated liver enzymesNausea/vomitingSerious adverse eventsAdvanced solid tumorsDose-escalation studyPI3K pathway inhibitionClass I PI3K isoformsTumor growth inhibitionPI3K pathwayPharmacodynamic modulationQD regimenStable diseaseBID regimenHepatic transaminasesNeurological complaintsRepeat dosingPI3K isoformsPlasma insulinTolerable doses
2008
216 POSTER A phase I dose-escalation study of the safety, pharmacokinetics and pharmacodynamics of XL765, a novel inhibitor of PI3K and mTOR, administered orally to patients with solid tumors
Markman B, LoRusso P, Patnaik A, Heath E, Laird A, van Leeuwen B, Papadopoulos K, Baselga J. 216 POSTER A phase I dose-escalation study of the safety, pharmacokinetics and pharmacodynamics of XL765, a novel inhibitor of PI3K and mTOR, administered orally to patients with solid tumors. European Journal Of Cancer Supplements 2008, 6: 68-69. DOI: 10.1016/s1359-6349(08)72148-7.Peer-Reviewed Original ResearchA phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel PI3K inhibitor, XL765, administered orally to patients (pts) with advanced solid tumors
Papadopoulos K, Markman B, Tabernero J, Patnaik A, Heath E, DeCillis A, Laird D, Aggarwal S, Nguyen L, LoRusso P. A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel PI3K inhibitor, XL765, administered orally to patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2008, 26: 3510-3510. DOI: 10.1200/jco.2008.26.15_suppl.3510.Peer-Reviewed Original Research
2007
A phase I study of BMS-582664 (brivanib alaninate), an oral dual inhibitor of VEGFR and FGFR tyrosine kinases, in combination with full-dose cetuximab in patients (pts) with advanced gastrointestinal malignancies (AGM) who failed prior therapy
Garrett C, Siu L, Giaccone G, El-Khoueiry A, Marshall J, LoRusso P, Velasquez L, Kollia G, He P, Feltquate D. A phase I study of BMS-582664 (brivanib alaninate), an oral dual inhibitor of VEGFR and FGFR tyrosine kinases, in combination with full-dose cetuximab in patients (pts) with advanced gastrointestinal malignancies (AGM) who failed prior therapy. Journal Of Clinical Oncology 2007, 25: 14018-14018. DOI: 10.1200/jco.2007.25.18_suppl.14018.Peer-Reviewed Original ResearchAdvanced gastrointestinal malignanciesFDG-PETColorectal cancerDay 8Phase I dose-escalation studyI dose-escalation studyPre-treatment FDG-PETDual tyrosine kinase inhibitorBilateral pulmonary emboliOral dual inhibitorPO day 1Treatment-related AEsFDG-PET resultsDose-escalation studyTyrosine kinase inhibitorsReproducible imaging modalityPrior therapyExpansion cohortGastrointestinal malignanciesPulmonary emboliDose escalationIntra-subject CVOral prodrugTumor responseTarget lesions
2006
648 POSTER A phase I dose-escalation study of weekly IMC-A12, a fully human insulin like growth factor-I receptor (IGF-IR) IgG1 monoclonal antibody (Mab), in patients (pts) with advanced cancer
Higano C, Gordon M, LoRusso P, Fox F, Katz T, Roecker J, Rowinsky E, Youssoufian H. 648 POSTER A phase I dose-escalation study of weekly IMC-A12, a fully human insulin like growth factor-I receptor (IGF-IR) IgG1 monoclonal antibody (Mab), in patients (pts) with advanced cancer. European Journal Of Cancer Supplements 2006, 4: 195. DOI: 10.1016/s1359-6349(06)70653-x.Peer-Reviewed Original Research