2023
Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma
Fanucci K, Pilat M, Shyr D, Shyr Y, Boerner S, Li J, Durecki D, Drappatz J, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma. Cancer Research Communications 2023, 3: 192-201. PMID: 36968138, PMCID: PMC10035510, DOI: 10.1158/2767-9764.crc-22-0436.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBrain NeoplasmsGliomaHumansIsocitrate DehydrogenaseNeoplasm Recurrence, LocalPoly(ADP-ribose) Polymerase InhibitorsConceptsProgression-free survivalMedian progression-free survivalProlonged stable diseaseStable diseasePhase II trialGrade 4 tumorsII trialOlaparib monotherapyGrade 2Multicenter phase 2 trialSingle-arm phase II trialWorld Health Organization classificationMedian overall survivalNeuro-Oncology criteriaPhase 2 trialOverall response rateFuture patient stratificationMutant gliomasPARP inhibitor olaparibEvaluable patientsPrimary endpointOverall survivalProgressive diseaseSelect patientsClinical benefit
2018
A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors
Ferrarotto R, Eckhardt G, Patnaik A, LoRusso P, Faoro L, Heymach J, Kapoun A, Xu L, Munster P. A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors. Annals Of Oncology 2018, 29: 1561-1568. PMID: 29726923, DOI: 10.1093/annonc/mdy171.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCohort StudiesDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalNeoplasmsPrognosisReceptor, Notch1Salvage TherapySurvival RateTissue DistributionConceptsNotch1 pathway activationPartial responseSolid tumorsPathway activationAdverse eventsCommon drug-related adverse eventsDrug-related adverse eventsDose-expansion studyGrade 3 diarrheaGrade 3 fatigueUnconfirmed partial responseRefractory solid tumorsProlonged SDsDisease stabilizationExpansion cohortMain toxicityRECIST 1.1Dose escalationEfficacy signalsClinical benefitPharmacodynamic effectsPreliminary efficacyAssessable subjectsImmunohistochemistry assaysNonlinear pharmacokinetics
2017
A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors
Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmaña J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clinical Cancer Research 2017, 23: 4095-4106. PMID: 28264872, DOI: 10.1158/1078-0432.ccr-16-2796.Peer-Reviewed Original ResearchConceptsHigh-grade ovarian carcinomaObjective response rateInvestigator-assessed objective response rateOral rucaparibAdverse eventsCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsAspartate transaminase elevationsAsthenia/fatigueProtocol-defined criteriaRECIST version 1.1Phase II doseAdvanced solid tumorsProgression-free intervalSmall molecule PARP inhibitorsClin Cancer ResManageable toxicityPrior regimensPrimary endpointTransaminase elevationPlatinum therapyMultiple dosesOvarian carcinomaAlanine transaminaseClinical activity
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