2024
603O First clinical results from a phase I trial of PRT3789: A first-in-class intravenous SMARCA2 degrader, in patients with advanced solid tumors with a SMARCA4 mutation
Guo R, Dowlati A, Dagogo-Jack I, Vibert J, Spira A, Garcia V, Punekar S, Calvo E, Sonpavde G, Awad M, Riess J, Guerrero T, Herzberg B, Italiano A, Swalduz A, Lorusso P, Smit E, Garon E, Novotny W, Yap T. 603O First clinical results from a phase I trial of PRT3789: A first-in-class intravenous SMARCA2 degrader, in patients with advanced solid tumors with a SMARCA4 mutation. Annals Of Oncology 2024, 35: s483-s484. DOI: 10.1016/j.annonc.2024.08.670.Peer-Reviewed Original ResearchFirst-in-human phase I trial of the oral first-in-class ubiquitin specific peptidase 1 (USP1) inhibitor KSQ-4279 (KSQi), given as single agent (SA) and in combination with olaparib (OLA) or carboplatin (CARBO) in patients (pts) with advanced solid tumors, enriched for deleterious homologous recombination repair (HRR) mutations.
Yap T, Lakhani N, Patnaik A, Lee E, Gutierrez M, Moore K, Carneiro B, Hays J, Huang M, LoRusso P, Wylie A, Cadzow L, Goulet M, Tobin E, Krieter O, Schmid D, Blake S, Dieterich M, Jamois C, Harris P. First-in-human phase I trial of the oral first-in-class ubiquitin specific peptidase 1 (USP1) inhibitor KSQ-4279 (KSQi), given as single agent (SA) and in combination with olaparib (OLA) or carboplatin (CARBO) in patients (pts) with advanced solid tumors, enriched for deleterious homologous recombination repair (HRR) mutations. Journal Of Clinical Oncology 2024, 42: 3005-3005. DOI: 10.1200/jco.2024.42.16_suppl.3005.Peer-Reviewed Original ResearchUbiquitin specific peptidase 1Treatment-emergent adverse eventsHomologous recombination repair mutationsSingle agentPARP inhibitorsHomologous recombination repairFirst-in-human phase I trialPreliminary anti-tumor activityPaired tumor biopsiesTNBC PDX modelsDisease control ratePhase I trialAUC 4Olaparib concentrationsRECIST PRDose escalationExpansion cohortCancer ptsDose proportionalityTumor biopsiesI trialMaculopapular rashPDX modelsDiscontinued treatmentDNA damage response pathway
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 time
2018
428P Interim results from a phase I trial of SL-801: A novel XPO-1 inhibitor, in patients with advanced solid tumors
Bauer T, Barve M, Chiorean E, Lorusso P, Courtney K, Qi D, Olguin A, Bullington J, Sardone M, Dunn V, Shemesh S, Chen J, Brooks C, Wang J. 428P Interim results from a phase I trial of SL-801: A novel XPO-1 inhibitor, in patients with advanced solid tumors. Annals Of Oncology 2018, 29: viii140. DOI: 10.1093/annonc/mdy279.415.Peer-Reviewed Original Research
2016
ACTR-10. PHASE 0 TRIAL OF AZD1775 IN FIRST-RECURRENCE GLIOBLASTOMA PATIENTS
Sanai N, Li J, Boerner J, Dhruv H, Berens M, LoRusso P. ACTR-10. PHASE 0 TRIAL OF AZD1775 IN FIRST-RECURRENCE GLIOBLASTOMA PATIENTS. Neuro-Oncology 2016, 18: vi3-vi3. DOI: 10.1093/neuonc/now212.009.Peer-Reviewed Original ResearchPhase 0 trialsInterindividual variabilityGlioblastoma patientsPhase II studyApparent oral clearanceGlomerular filtration ratePhase I trialCL/F.CL/FSparse blood samplingElimination rate constantAbsorption rate constantPD endpointsAdult patientsII studyOral clearanceI trialSingle doseDrug exposureFiltration ratePreclinical modelsPreclinical studiesGlioma patientsPlasma ratioBlood sampling
2013
Clinical and pharmacodynamic (PD) results of a phase I trial with AMP-224 (B7-DC Fc) that binds to the PD-1 receptor.
Infante J, Powderly J, Burris H, Kittaneh M, Grice J, Smothers J, Brett S, Fleming M, May R, Marshall S, Devenport M, Pillemer S, Pardoll D, Chen L, Langermann S, LoRusso P. Clinical and pharmacodynamic (PD) results of a phase I trial with AMP-224 (B7-DC Fc) that binds to the PD-1 receptor. Journal Of Clinical Oncology 2013, 31: 3044-3044. DOI: 10.1200/jco.2013.31.15_suppl.3044.Peer-Reviewed Original ResearchPD-1B7-H1T cellsFunctional T cell responsesT cell effector functionPK/PD relationshipInflammatory adverse eventsPD-1 axisAdvanced solid tumorsPre-treatment biopsiesTumor immune evasionPhase I trialT cell poolT cell responsesInitial disease progressionPD-1 receptorCell effector functionsFunctional T cellsMultiple tumor typesBaseline tumorPD-1highStable diseaseB7-DCLymphocyte subsetsAdverse events
2012
Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy.
Alsina M, Tabernero J, Shapiro G, Burris H, Infante J, Weiss G, Cervantes-Ruiperez A, Gounder M, Paz-Ares L, Falzone R, Hill J, Cehelsky J, Vaishnaw A, Gollob J, LoRusso P. Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy. Journal Of Clinical Oncology 2012, 30: 3062-3062. DOI: 10.1200/jco.2012.30.15_suppl.3062.Peer-Reviewed Original ResearchStable diseasePartial responseExtension studyAdverse eventsEndometrial cancerCancer patientsCell carcinomaOpen-label extension studyNeck squamous cell carcinomaMore prior therapiesOngoing partial responseSafety/tolerabilityUnconfirmed partial responseEndometrial cancer patientsPhase II trialMonths of treatmentPhase I trialPhase 1 trialFavorable safety profileSquamous cell carcinomaTime of enrollmentPancreatic neuroendocrine tumorsVascular endothelial growth factorYears of treatmentRenal cell carcinoma
2010
Hyperglycemia, hypertriglyceridemia, and hypercholesterolemia in a phase I trial of the combination of an mTOR inhibitor and IGF-1 receptor inhibitor.
Busaidy N, Kurzrock R, LoRusso P, Owens A, Chen H, Doyle L, Zhang J, Lawhorn K, Chandhasin C, Naing A. Hyperglycemia, hypertriglyceridemia, and hypercholesterolemia in a phase I trial of the combination of an mTOR inhibitor and IGF-1 receptor inhibitor. Journal Of Clinical Oncology 2010, 28: 2597-2597. DOI: 10.1200/jco.2010.28.15_suppl.2597.Peer-Reviewed Original Research
2009
Population Pharmacokinetics of Trastuzumab-DM1, a First-in-Class HER2 Antibody-Drug Conjugate Given Every 3 Weeks (q3w) and Weekly (qw) to Patients with HER2-Positive Metastatic Breast Cancer (MBC).
LoRusso P, Girish S, Burris H, Beeram M, Vukelja S, Modi S, Yi J, Wang B, Saad O, Gupta M. Population Pharmacokinetics of Trastuzumab-DM1, a First-in-Class HER2 Antibody-Drug Conjugate Given Every 3 Weeks (q3w) and Weekly (qw) to Patients with HER2-Positive Metastatic Breast Cancer (MBC). Cancer Research 2009, 69: 5099-5099. DOI: 10.1158/0008-5472.sabcs-09-5099.Peer-Reviewed Original ResearchMetastatic breast cancerHER2-positive metastatic breast cancerHER2 antibody-drug conjugatesPhase II trialT-DM1Antibody-drug conjugatesII trialClinical factorsInter-individual variabilityTumor burdenIndividual patientsCovariate analysisPK parametersPK dataPK modelOngoing phase II trialSubsequent phase II trialTwo-compartment linear modelPhase I trialPopulation PK modelPopulation pharmacokinetic modelMultiple dose levelsConcentration-time dataAvailable PK dataPK parameter valuesPharmacogenetics of a PARP inhibitor ABT-888 metabolic pathway
Li J, Sha X, LoRusso P. Pharmacogenetics of a PARP inhibitor ABT-888 metabolic pathway. Journal Of Clinical Oncology 2009, 27: e14556-e14556. DOI: 10.1200/jco.2009.27.15_suppl.e14556.Peer-Reviewed Original ResearchGenetic variantsMetabolic pathwaysDNA break repairABT-888Significant genetic variantsTherapeutic outcomesBreak repairCytochrome P450Ongoing phase I trialMolecular basisWild-type CYP2D6Advanced solid tumorsPhase I trialRecombinant human cytochrome P450DNA damageHuman liver microsomesMetabolite formationVariant enzymeMultiple cytotoxic agentsTumor drug concentrationsPARP activityFunctional significanceMajor enzymePredominant enzymeHuman cytochrome P450
2007
A phase I study of EC145 administered weeks 1 and 3 of a 4-week cycle in patients with refractory solid tumors
Sausville E, LoRusso P, Quinn M, Forman K, Leamon C, Morganstern D, Bever S, Messmann R. A phase I study of EC145 administered weeks 1 and 3 of a 4-week cycle in patients with refractory solid tumors. Journal Of Clinical Oncology 2007, 25: 2577-2577. DOI: 10.1200/jco.2007.25.18_suppl.2577.Peer-Reviewed Original ResearchBolus dosesDay 1Folate receptorPhase IRefractory solid tumorsCommon side effectsFolic acidPhase I trialTime of presentationIntravenous bolus doseEligible patientsDisease stabilizationFlat doseI trialIntravenous bolusBolus doseMinor responsePK analysisSide effectsPatientsWeek 1Dose levelsEscalation plansSolid tumorsPK modelPhase 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 patientsA phase I, first in man study of weekly IMC-A12, a fully human insulin like growth factor-I receptor IgG1 monoclonal antibody, in patients with advanced solid tumors
Higano C, Yu E, Whiting S, Gordon M, LoRusso P, Fox F, Katz T, Roecker J, Schwartz J. A phase I, first in man study of weekly IMC-A12, a fully human insulin like growth factor-I receptor IgG1 monoclonal antibody, in patients with advanced solid tumors. Journal Of Clinical Oncology 2007, 25: 3505-3505. DOI: 10.1200/jco.2007.25.18_suppl.3505.Peer-Reviewed Original ResearchIMC-A12IgG1 monoclonal antibodySolid tumorsAdvanced refractory solid tumorsHuman anti-human antibodiesMedian age 56 yearsMonoclonal antibodiesNon-compartmental PK analysisGrade 2 anemiaGrade 3 hyperglycemiaHuman IgG1 monoclonal antibodyStable radiographic diseaseTreatment related toxicityInfusion-related reactionsAdvanced solid tumorsAge 56 yearsRefractory solid tumorsHuman insulinPhase I trialWeek observation periodAnti-human antibodiesDiscolored fecesECOG PSStable diseaseStudy discontinuation
2006
644 POSTER The novel oral taxane BMS275183 has a favorable activity and toxicity profile in a twice weekly schedule; Preliminary findings from an extended phase I trial
Bröker L, Veltkamp S, Heath E, Gall H, Kuenen B, Voi M, Kayitalire L, Lorusso P, Schellens J, Giaccone G. 644 POSTER The novel oral taxane BMS275183 has a favorable activity and toxicity profile in a twice weekly schedule; Preliminary findings from an extended phase I trial. European Journal Of Cancer Supplements 2006, 4: 194. DOI: 10.1016/s1359-6349(06)70649-8.Peer-Reviewed Original ResearchPhase I evaluation of AZD2171, a highly potent and selective inhibitor of VEGFR signaling, in combination with selected chemotherapy regimens in patients with advanced solid tumors
Lorusso P, Heath E, Valdivieso M, Pilat M, Wozniak A, Gadgeel S, Shields A, Puchalski T, Ewesuedo R. Phase I evaluation of AZD2171, a highly potent and selective inhibitor of VEGFR signaling, in combination with selected chemotherapy regimens in patients with advanced solid tumors. Journal Of Clinical Oncology 2006, 24: 3034-3034. DOI: 10.1200/jco.2006.24.18_suppl.3034.Peer-Reviewed Original ResearchVascular endothelial growth factor receptorDose-limiting toxicityArm 1Chemotherapy regimensArm 2Arm 4Grade 3 hand-foot syndromeSolid tumorsGrade 4 neutropenic feverGrade 3 diarrheaGrade 3 fatigueGrade 3 hypertensionHand-foot syndromePhase I evaluationPre-treated patientsAdvanced solid tumorsPhase I trialEndothelial growth factor receptorSolid tumor patientsDuration of responseSelective inhibitorEfficacy/toxicityGrowth factor receptorIdentical chemotherapyNeutropenic fever
2005
A phase I trial of SR271425 given as a one hour infusion every 3 weeks to patients with advanced solid tumors
Wadler S, Loh E, Pilat M, Malburg L, Holloway S, Matthews N, Shackleton G, Valdivieso M, Lorusso P. A phase I trial of SR271425 given as a one hour infusion every 3 weeks to patients with advanced solid tumors. Journal Of Clinical Oncology 2005, 23: 2030-2030. DOI: 10.1200/jco.2005.23.16_suppl.2030.Peer-Reviewed Original ResearchA phase I trial investigating a twice weekly administration of the oral taxane BMS-275183 in patients with advanced solid tumors
Broker L, Ruyter R, Voi M, Woo M, Astier L, Heath E, Lorusso P, Giaccone G. A phase I trial investigating a twice weekly administration of the oral taxane BMS-275183 in patients with advanced solid tumors. Journal Of Clinical Oncology 2005, 23: 2040-2040. DOI: 10.1200/jco.2005.23.16_suppl.2040.Peer-Reviewed Original Research
2000
Objective regressions in non-small cell lung cancer patients treated in Phase I trials of oral ZD1839 (IressaTM), a selective tyrosine kinase inhibitor that blocks the epidermal growth factor receptor (EGFR)
Kris M, Herbst R, Rischin D, LoRusso P, Baselga J, Hammond L, Feyereislova A, Ochs J, Averbuch S. Objective regressions in non-small cell lung cancer patients treated in Phase I trials of oral ZD1839 (IressaTM), a selective tyrosine kinase inhibitor that blocks the epidermal growth factor receptor (EGFR). Lung Cancer 2000, 29: 72. DOI: 10.1016/s0169-5002(00)80233-0.Peer-Reviewed Original ResearchEpidermal growth factor receptorNon-small cell lung cancer patientsCell lung cancer patientsPhase I trialSelective tyrosine kinase inhibitorLung cancer patientsTyrosine kinase inhibitorsGrowth factor receptorObjective regressionI trialCancer patientsOral ZD1839Kinase inhibitorsFactor receptorPatientsZD1839
1996
Preclinical antitumor activity of CI-994
LoRusso P, Demchik L, Foster B, Knight J, Bissery M, Polin L, Leopold W, Corbett T. Preclinical antitumor activity of CI-994. Investigational New Drugs 1996, 14: 349-356. PMID: 9157069, DOI: 10.1007/bf00180810.Peer-Reviewed Original ResearchConceptsCI-994Prolonged administrationMammary adenocarcinomaClinical phase I trialColon adenocarcinomaPhase I trialHuman xenograft tumor modelsDays of administrationIndividual dosesPancreatic ductal adenocarcinomaPreclinical antitumor activityShort-term therapyLower drug dosesXenograft tumor modelHigher individual dosesI trialOsteogenic sarcomaDuctal adenocarcinomaNovel antitumor agentsDrug dosesAdenocarcinomaSolid tumorsTotal doseGross toxicityTumor model
1995
Phase I trial of Adozelesin using the treatment schedule of daily × 5 every 3 weeks
Foster B, LoRusso P, Poplin E, Zalupski M, Valdivieso M, Wozniak A, Flaherty L, Kasunic D, Earhart R, Baker L. Phase I trial of Adozelesin using the treatment schedule of daily × 5 every 3 weeks. Investigational New Drugs 1995, 13: 321-326. PMID: 8824350, DOI: 10.1007/bf00873138.Peer-Reviewed Original ResearchConceptsMinute IV infusionTreatment scheduleM2/dayIV infusionPhase II starting doseRefractory soft tissue sarcomasConsecutive daysPhase IUnique alkylating agentRefractory solid tumorsPhase I trialSoft tissue sarcomasAdditional phase IPreclinical toxicology studiesBroad antitumor activityPotent synthetic analogsAnaphylactoid syndromeStarting doseI trialPartial responseAntitumor responseCumulative myelosuppressionTissue sarcomasTherapeutic dosesCytotoxic treatment