2022
Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and in combination with PD-1 inhibitors nivolumab or dostarlimab (AMBER).
Falchook G, Ribas A, Davar D, Eroglu Z, Wang J, Luke J, Hamilton E, Di Pace B, Wang T, Ghosh S, Dhar A, Borgovan T, Waszak A, LoRusso P. Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and in combination with PD-1 inhibitors nivolumab or dostarlimab (AMBER). Journal Of Clinical Oncology 2022, 40: 2504-2504. DOI: 10.1200/jco.2022.40.16_suppl.2504.Peer-Reviewed Original ResearchTreatment-related treatment-emergent adverse eventsNon-small cell lung cancerPD-1 inhibitor nivolumabTreatment-emergent adverse eventsTumor-infiltrating T cellsPreliminary anti-tumor activityPhase 2 doseOpen-label studyPD-1 inhibitorsAdvanced solid tumorsPhase 2 studyDose-proportional mannerPhase 1 trialT cell suppressionCell lung cancerTherapeutic dose rangeMost common cancersAnti-tumor activityDose delaysPrior therapyInhibitor nivolumabPrimary endpointTim-3Adverse eventsPeritoneal mesotheliomaPraluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial
Boni V, Fidler MJ, Arkenau HT, Spira A, Meric-Bernstam F, Uboha N, Sanborn RE, Sweis RF, LoRusso P, Nagasaka M, Garcia-Corbacho J, Jalal S, Harding JJ, Kim SK, Miedema IHC, Vugts DJ, Huisman MC, Zwezerijnen GJC, van Dongen GAMS, van Oordt C, Wang S, Dang T, Zein IA, Vasiljeva O, Lyman SK, Paton V, Hannah A, Liu JF. Praluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial. Clinical Cancer Research 2022, 28: 2020-2029. PMID: 35165101, PMCID: PMC9365353, DOI: 10.1158/1078-0432.ccr-21-3656.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsOpen-label phase I/II trialSolid tumorsPhase I/II trialPhase I/II clinical trialsBasis of tolerabilityPhase II doseBreast cancer subsetsAntibody-drug conjugatesProtease-cleavable linkerEligible patientsPosttreatment biopsiesPrior therapyStable diseaseII trialPartial responseSafety profileTumor regressionClinical trialsPrevalent subtypeCancer subsetsClinical activityMetastatic cancerBreast cancerMedian number
2020
CX-2009, a CD166-directed probody drug conjugate (PDC): Results from the first-in-human study in patients (Pts) with advanced cancer including breast cancer (BC).
Boni V, Burris III H, Liu J, Spira A, Arkenau H, Fidler M, Rosen L, Sweis R, Uboha N, Sanborn R, O'Neil B, Harding J, LoRusso P, Weise A, Garcia-Corbacho J, Victoria I, Frye J, Li R, Stroh M, Meric-Bernstam F. CX-2009, a CD166-directed probody drug conjugate (PDC): Results from the first-in-human study in patients (Pts) with advanced cancer including breast cancer (BC). Journal Of Clinical Oncology 2020, 38: 526-526. DOI: 10.1200/jco.2020.38.15_suppl.526.Peer-Reviewed Original ResearchTreatment-related adverse eventsBreast cancerQ3w scheduleAdvanced cancerGrade 3 treatment-related adverse eventsHuman studiesCommon treatment-related adverse eventsMultiple solid tumor modelsInfusion-related reactionsPhase II doseAdvanced solid tumorsDose-escalation phaseDose-escalation studyPhase II expansionClinical trial informationPopulation pharmacokinetic simulationsMicrotubule inhibitorsSolid tumor modelsTumor-associated proteasesCX-072Prior therapyQ2W dosingQ3W dosingAdverse eventsPartial response
2019
Phase 1a/1b study of first-in-class B7-H4 antibody, FPA150, as monotherapy in patients with advanced solid tumors.
Sachdev J, Bauer T, Chawla S, Pant S, Patnaik A, Wainberg Z, Inamdar S, Marina N, Sun S, Schmidt M, Xiang H, LoRusso P. Phase 1a/1b study of first-in-class B7-H4 antibody, FPA150, as monotherapy in patients with advanced solid tumors. Journal Of Clinical Oncology 2019, 37: 2529-2529. DOI: 10.1200/jco.2019.37.15_suppl.2529.Peer-Reviewed Original ResearchTreatment-related AEsAdvanced solid tumorsB7-H4Solid tumorsExploration cohortEndometrial cancerDose escalationTreatment-related serious adverse eventsAntibody-dependent cell-mediated cytotoxicityB7-H4 antibodyDose-proportional exposureSerious adverse eventsT cell activityCell-mediated cytotoxicityFavorable safety profileT cell functionAnti-tumor activityPreliminary biomarkerPrior therapyTreatment biopsiesAdverse eventsMost patientsSafety profileB7 familyEfficacy data
2013
Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma
Naing A, LoRusso P, Fu S, Hong D, Chen H, Doyle L, Phan A, Habra M, Kurzrock R. Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma. British Journal Of Cancer 2013, 108: 826-830. PMID: 23412108, PMCID: PMC3590681, DOI: 10.1038/bjc.2013.46.Peer-Reviewed Original ResearchConceptsIGF-1R inhibitorsAdrenocortical carcinomaStable diseaseAggressive endocrine malignancyHuman IgG1 monoclonal antibodyProlonged stable diseaseMetastatic adrenocortical carcinomaGrowth factor receptor antibodyEffective systemic chemotherapyMTOR inhibitor temsirolimusIGF-1 receptorIgG1 monoclonal antibodyFrequent toxicitiesPrior therapySystemic chemotherapyMedian ageReceptor antibodiesPreclinical dataEndocrine malignancyMedian numberIGF-1RPatientsTemsirolimusCixutumumabGrade 1
2012
Activity of insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic refractory adrenocortical carcinoma.
Naing A, LoRusso P, Fu S, Hong D, Chen H, Doyle L, Phan A, Habra M, Kurzrock R. Activity of insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic refractory adrenocortical carcinoma. Journal Of Clinical Oncology 2012, 30: 4639-4639. DOI: 10.1200/jco.2012.30.15_suppl.4639.Peer-Reviewed Original ResearchIGF-1R inhibitorsAdrenocortical carcinomaStable diseaseHuman IgG1 monoclonal antibodyProlonged stable diseaseGrowth factor receptor antibodyEffective systemic chemotherapyGrowth factor 1 receptorInsulin growth factor-1 receptorMTOR inhibitor temsirolimusFactor 1 receptorIgG1 monoclonal antibodyPrior therapyFrequent toxicitiesSystemic chemotherapyMedian agePreclinical dataMedian numberTemsirolimusPatientsCixutumumabMTOR pathwayGrade 1Monoclonal antibodiesCarcinoma
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 cancer
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
Phase-1 study of isophosphoramide mustard (IPM)-lysine in advanced cancers
Gale R, Van Vugt A, Rosen L, Chang L, Lorusso P, Valdivieso M, Malburg L, Struck R, Morgan L. Phase-1 study of isophosphoramide mustard (IPM)-lysine in advanced cancers. Journal Of Clinical Oncology 2006, 24: 9524-9524. DOI: 10.1200/jco.2006.24.18_suppl.9524.Peer-Reviewed Original ResearchCNS toxicityAdvanced cancerProximal renal tubular acidosisExtensive prior therapyHuman-mouse xenograftsPhase 1 studyPhase 1 trialRenal tubular acidosisPre-clinical modelsDiverse cancer modelsGI complaintsPrior therapyStable diseaseCancer cell linesLimited diseaseStarting doseHemorrhagic cystitisMedian ageColorectal cancerTubular acidosisThyroid cancerDose levelsCancer modelGreater efficacyHuman cancer cell lines