2020
Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies
Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clinical Cancer Research 2020, 26: 1247-1257. PMID: 31527168, PMCID: PMC7528620, DOI: 10.1158/1078-0432.ccr-18-4071.Peer-Reviewed Original ResearchConceptsAdvanced malignanciesGrade treatment-related adverse eventsTreatment-related adverse eventsAdequate organ functionHigh interpatient variabilityFavorable PK profileOptimal dosing schemePrimary endpointAdverse eventsOral clearancePartial responseComplete responsePhase 1/2Terminal eliminationTolerability studyPatient populationPharmacodynamic profileInterpatient variabilityDosing schemesDistinct pharmacokineticsTherapeutic indexOrgan functionPK profilesExtraterminal (BET) inhibitorsTarget inhibition
2019
A phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers.
Mobasher M, Miller R, Kwei L, Strahs D, Das V, Luciano G, Powderly J, Merchan J, Barve M, LoRusso P, Tripathi A, Luke J. A phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers. Journal Of Clinical Oncology 2019, 37: tps2646-tps2646. DOI: 10.1200/jco.2019.37.15_suppl.tps2646.Peer-Reviewed Original ResearchSingle agentCD73 antibodyTumor growthNon-small cell lungAdequate organ functionAnti-CD73 antibodiesOpen-label trialTreatment of patientsRenal cell carcinomaSelective A2AR antagonistNumber of malignanciesKnockout mice exhibitTriple-negative breastEligible patientsMeasurable diseaseLabel trialAdult patientsStandard therapyAdvanced cancerCD73 expressionImmunosuppressive adenosineMulticenter studyUrothelial bladderCell carcinomaCell lung
2015
Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer.
Kwak E, LoRusso P, Hamid O, Janku F, Kittaneh M, Catenacci D, Chan E, Bekaii-Saab T, Amore B, Hwang Y, Tang R, Ngarmchamnanrith G, Hong D. Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer. Journal Of Clinical Oncology 2015, 33: 1-1. DOI: 10.1200/jco.2015.33.3_suppl.1.Peer-Reviewed Original ResearchAMG 337MET kinase inhibitorGastroesophageal junctionGI cancersClinical activityCommon treatment-emergent AEsKinase inhibitorsAdequate organ functionDose-expansion phaseSubset of ptsTreatment-emergent AEsAdvanced solid tumorsDose-limiting toxicityKey eligibility criteriaAmplification/mutationMeasurable diseaseAdult patientsComplete responsePartial responseDose escalationMedian ageGI tumorsAE profileEsophageal cancerMET pathway
2013
A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC).
Goncalves P, Kummar S, Siu L, Hansen A, Savvides P, Sukari A, Chao J, Heilbrun L, Pilat M, Smith D, Casetta L, Boerner S, LoRusso P. A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC). Journal Of Clinical Oncology 2013, 31: 6045-6045. DOI: 10.1200/jco.2013.31.15_suppl.6045.Peer-Reviewed Original ResearchProgression-free survivalAdenoid cystic carcinomaSuberoylanilide hydroxamic acidMetastatic adenoid cystic carcinomaOverall survivalAdverse eventsResponse durationResponse rateEvaluable patientsOnly grade 3 adverse eventGrade 3 adverse eventsMedian progression-free survivalTreatment of ACCAdequate organ functionMedian overall survivalPhase II studyPhase II trialHistone deacetylasesDrug combination studiesChemo-naïveChemotherapy regimensII trialOral painSecondary endpointsThromboembolic events
2012
507 Phase I, Open-Label, Randomized, Crossover Study Evaluating the Effects of Linifanib on Qtc Intervals in Patients with Solid Tumors
Chiu Y, LoRusso P, Ricker J, Li X, Pradhan R, Carlson D. 507 Phase I, Open-Label, Randomized, Crossover Study Evaluating the Effects of Linifanib on Qtc Intervals in Patients with Solid Tumors. Annals Of Oncology 2012, 23: ix173. DOI: 10.1016/s0923-7534(20)33069-6.Peer-Reviewed Original ResearchAdvanced solid tumorsDay 1Solid tumorsCardiac repolarizationAdequate organ functionECOG PS 0Primary end pointExposure-response analysisEffects modelMeasurable diseaseMorning doseOpen labelCrossover fashionPS 0QTc prolongationStandard therapyCrossover studyQTc intervalBaseline QTcFQTcF intervalStudy completionSafety, pharmacokinetics, and antitumor activity of MEDI-573, an investigational monoclonal antibody that targets IGF-I and IGF-II, in adult patients with advanced solid tumors.
Haluska P, Menefee M, Plimack E, Rosenberg J, Northfelt D, LaVallee T, Huang W, Yu X, Viner J, LoRusso P. Safety, pharmacokinetics, and antitumor activity of MEDI-573, an investigational monoclonal antibody that targets IGF-I and IGF-II, in adult patients with advanced solid tumors. Journal Of Clinical Oncology 2012, 30: tps2618-tps2618. DOI: 10.1200/jco.2012.30.15_suppl.tps2618.Peer-Reviewed Original ResearchMEDI-573Advanced solid tumorsSolid tumorsAdult patientsGlucose homeostasisDose levelsDrug-related adverse eventsMedian age 64 yearsAdequate organ functionIGF-I/-IIInvestigational monoclonal antibodyAntitumor activityAcceptable safety profileAdvanced bladder cancerAge 64 yearsKarnofsky statusQ3W dosingStable diseaseAdverse eventsSafety profileIGF-IIBladder cancerSerum glucoseSerious toxicityIGF-1R
2007
Phase I trial of intravenous 17-allylaminogeldanamycin (A) and oral sorafenib (B) in pretreated advanced malignancy: Plasma Hsp90α induction correlates with clinical benefit
Vaishampayan U, Sausville E, Horiba M, Quinn M, Heilbrun L, Burger A, Ivy P, Li J, Lorusso P. Phase I trial of intravenous 17-allylaminogeldanamycin (A) and oral sorafenib (B) in pretreated advanced malignancy: Plasma Hsp90α induction correlates with clinical benefit. Journal Of Clinical Oncology 2007, 25: 3531-3531. DOI: 10.1200/jco.2007.25.18_suppl.3531.Peer-Reviewed Original ResearchAdvanced malignanciesClinical benefitGrade 3 hand-foot syndromeAdequate organ functionGrade 2 nauseaGrade 3 fatigueResponse-evaluable patientsHand-foot syndromePhase II dosePhase I trialSystemic cancer therapyDose cohortsEvaluable patientsInevaluable patientsNCI-CTEPOral sorafenibStable diseaseB. PatientsClinical responseFoot syndromeLatter patientsMajor toxicityPartial responsePerformance statusStable patients