2024
A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170)
Maldonado E, Rathmell W, Shapiro G, Takebe N, Rodon J, Mahalingam D, Trikalinos N, Kalebasty A, Parikh M, Boerner S, Balido C, Krings G, Burns T, Bergsland E, Munster P, Ashworth A, LoRusso P, Aggarwal R. A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170). Cancer Research Communications 2024, 4: 1793-1801. PMID: 38920407, PMCID: PMC11264598, DOI: 10.1158/2767-9764.crc-24-0213.Peer-Reviewed Original ResearchSolid tumor malignanciesStable diseaseTumor malignancyAdverse eventsDepth of tumor responseLoss of H3K36me3Median duration of treatmentAdvanced solid tumor malignanciesClear cell renal cell carcinomaMinor tumor regressionsProlonged stable diseaseArchival tumor tissuePhase II studyCell renal cell carcinomaPhase II trialRenal cell carcinomaDuration of treatmentArchival tissue samplesSimon's two-stageTumor responseTumor regressionII trialMedian durationII studySETD2 mutationsA phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer.
Mukohara T, Park Y, Sommerhalder D, Yonemori K, Kim S, Kim J, Iwata H, Yamashita T, Layman R, Kim G, Im S, Lindeman G, Rugo H, Liyanage M, Homji Mishra N, Maity A, Bogg O, Liu L, Li M, LoRusso P. A phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer. Journal Of Clinical Oncology 2024, 42: 3006-3006. DOI: 10.1200/jco.2024.42.16_suppl.3006.Peer-Reviewed Original ResearchHER2- metastatic breast cancerTreatment-related adverse eventsMetastatic breast cancerCirculating tumor DNABreast cancerGene mutationsFrequent treatment-related adverse eventsMedian duration of follow-upAntitumor activityDuration of follow-upClinical benefit rateProgression-free survivalHER2 breast cancerMutant allele frequencyExpansion doseFulvestrant combinationMedian DoRESR1 mutationsMetastatic settingDose modificationEndocrine therapySystemic therapyMedian durationTumor DNACDK4/6 inhibitors
2023
Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial
Desai J, Alonso G, Kim S, Cervantes A, Karasic T, Medina L, Shacham-Shmueli E, Cosman R, Falcon A, Gort E, Guren T, Massarelli E, Miller W, Paz-Ares L, Prenen H, Amatu A, Cremolini C, Kim T, Moreno V, Ou S, Passardi A, Sacher A, Santoro A, Stec R, Ulahannan S, Arbour K, Lorusso P, Luo J, Patel M, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Jun T, Dharia N, Schutzman J, Han S. Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial. Nature Medicine 2023, 30: 271-278. PMID: 38052910, PMCID: PMC10803265, DOI: 10.1038/s41591-023-02696-8.Peer-Reviewed Original ResearchPhase 1b trialColorectal cancerSafety profileMedian progression-free survivalTreatment-related adverse eventsInhibitor-naive patientsKRAS G12C inhibitionAntitumor activityManageable safety profileObjective response rateProgression-free survivalPreliminary antitumor activityKRAS G12C mutationKRAS G12C inhibitorsEpidermal growth factor receptorVariant allele frequencyGrowth factor receptorAdverse eventsMedian durationTreatment withdrawalPoor prognosisDisease progressionArm CDose reductionG12C inhibitors
2022
Interim safety and efficacy results from AURELIO-03: A phase 1 dose escalation study of the IL-2/IL-15 receptor βγ superagonist SOT101 as a single agent and in combination with pembrolizumab in patients with advanced solid tumors.
Garralda E, Naing A, Galvao V, LoRusso P, Grell P, Cassier P, Gomez-Roca C, Korakis I, Bechard D, Jelinkova L, Adkins I, Tillmanns S, Kiemle-Kallee J, Marabelle A, Champiat S. Interim safety and efficacy results from AURELIO-03: A phase 1 dose escalation study of the IL-2/IL-15 receptor βγ superagonist SOT101 as a single agent and in combination with pembrolizumab in patients with advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 2502-2502. DOI: 10.1200/jco.2022.40.16_suppl.2502.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsClinical benefit rateAdvanced solid tumorsPartial responseStable diseaseMedian durationComplete responseClinical benefitBenefit rateAnti-programmed cell death protein 1 antibodyCommon treatment-emergent adverse eventsSolid tumorsMost treatment-emergent adverse eventsPhase 1 dose-escalation studyCell death protein 1 antibodyIL-15 receptor αSkin squamous cell carcinomaIL-2/ILFirst tumor assessmentOngoing complete responsePhase 2 dosePromising efficacy signalsTreatment-related deathsDose-escalation studyPhase 1 study
2021
A phase Ib study of xentuzumab plus abemaciclib and fulvestrant in patients (pts) with advanced hormone receptor-positive (HR+), HER2-negative breast cancer (BC) with visceral or non-visceral disease.
Yee D, LoRusso P, Sablin M, Prat A, Stradella A, Utriainen M, Oliveira M, Yonemori K, Naito Y, Hardebeck M, Puig M, Hu J, Biyukov T, Iwata H. A phase Ib study of xentuzumab plus abemaciclib and fulvestrant in patients (pts) with advanced hormone receptor-positive (HR+), HER2-negative breast cancer (BC) with visceral or non-visceral disease. Journal Of Clinical Oncology 2021, 39: 1057-1057. DOI: 10.1200/jco.2021.39.15_suppl.1057.Peer-Reviewed Original ResearchDisease control rateNon-visceral diseaseEndocrine therapyBreast cancerVisceral metastasesProgression-free survival benefitHER2-negative breast cancerDisease controlDose-finding cohortMost common AEsMedian treatment durationOpen-label studyPhase Ib studyPhase II doseNon-measurable diseaseHypo/hyperglycemiaCyclin-dependent kinase 4Advanced hormoneCommon AEsPFS ratesExpansion cohortPostmenopausal womenPrimary endpointSecondary endpointsMedian durationA first-in-human study of mirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose escalation results.
Tolcher A, Carneiro B, Dowlati A, Razak A, Chae Y, Villella J, Coppola S, Englert S, Phillips A, Souers A, Salman Z, Penugonda S, Powderly J, LoRusso P. A first-in-human study of mirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose escalation results. Journal Of Clinical Oncology 2021, 39: 3015-3015. DOI: 10.1200/jco.2021.39.15_suppl.3015.Peer-Reviewed Original ResearchRefractory solid tumorsAdverse eventsCell lung cancerSolid tumorsLymphocyte countLung cancerNon-small cell lung cancerSmall cell lung cancerMedian age 62 yearsCommon adverse eventsDose-expansion phasePhase 2 dosePrior systemic therapyTolerable safety profileFatal adverse eventsFatal cardiac arrestOverall response rateAge 62 yearsDose-escalation resultsAnti-tumor activityECOG 0ECOG 1RECIST v1.1Taxane therapyMedian duration
2019
457P First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumours: Dose-optimization cohorts
Calvo E, de Jonge M, Rasco D, Moreno V, Chang Y, Chiney M, Motwani M, Penugonda S, Petrich A, Ratain M, LoRusso P. 457P First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumours: Dose-optimization cohorts. Annals Of Oncology 2019, 30: v169-v170. DOI: 10.1093/annonc/mdz244.019.Peer-Reviewed Original ResearchDose levelsPancreatic cancerNon-cardiac chest painGenentech/RochePhase 2 dosePrior treatment regimensAntitumor activityAcceptable safety profileDose-limiting toxicityRoche/GenentechDeath receptor 4Bristol-Myers SquibbEligible ptsPleuritic painStable diseaseChest painGrade 3/4Respiratory failureMedian durationPartial responseToxic hepatitisDose escalationTreatment regimensSafety profileConclusion AdministrationPhase 1, first-in-human study of TRAIL receptor agonist fusion protein ABBV-621.
Ratain M, Doi T, De Jonge M, LoRusso P, Dunbar M, Chiney M, Motwani M, Glasgow J, Petrich A, Rasco D, Calvo E. Phase 1, first-in-human study of TRAIL receptor agonist fusion protein ABBV-621. Journal Of Clinical Oncology 2019, 37: 3013-3013. DOI: 10.1200/jco.2019.37.15_suppl.3013.Peer-Reviewed Original ResearchDose escalationDose-limiting toxicityBlood-based markersECOG 0Prior regimensStable diseaseAcceptable toxicityMedian durationRespiratory failureMedian agePartial responseColorectal cancerPancreatic cancerBlood bilirubinBayesian continual reassessment methodPD markersContinual reassessment methodHuman studiesDay 1Solid tumorsTumor typesPK studiesTumor modelAntitumor activityApoptotic cell deathPhase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors
Hong DS, LoRusso P, Hamid O, Janku F, Kittaneh M, Catenacci DVT, Chan E, Bekaii-Saab T, Gadgeel S, Loberg RD, Amore BM, Hwang YC, Tang R, Ngarmchamnanrith G, Kwak EL. Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors. Clinical Cancer Research 2019, 25: 2403-2413. PMID: 30425090, PMCID: PMC6892342, DOI: 10.1158/1078-0432.ccr-18-1341.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsAdvanced solid tumorsAMG 337Adverse eventsFrequent treatment-related adverse eventsResponse rateSolid tumorsOpen-label phase ISmall-molecule MET inhibitorDose-escalation cohortsObjective response ratePhase II dosePromising response ratesDose-limiting toxicityMaximum plasma concentrationTumors warrants further investigationWarrants further investigationManageable toxicityDose expansionPrimary endpointSecondary endpointsDaily dosingMedian durationClinical responseMET inhibitors
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
1999
Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer.
Blum J, Jones S, Buzdar A, LoRusso P, Kuter I, Vogel C, Osterwalder B, Burger H, Brown C, Griffin T. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. Journal Of Clinical Oncology 1999, 17: 485-93. PMID: 10080589, DOI: 10.1200/jco.1999.17.2.485.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerTreatment-related adverse eventsHand-foot syndromeBreast cancerAdverse eventsCommon treatment-related adverse eventsLarge multicenter phase II trialOnly treatment-related adverse eventMulticenter phase II studyMulticenter phase II trialComplete response durationPrior chemotherapeutic regimensPhase II studyPhase II trialMedian survival timeFavorable toxicity profileOverall response rateFluoropyrimidine carbamateMeasurable diseaseOral capecitabineAssessable diseaseII trialII studyMedian durationMetastatic disease
1989
Low-Dose Continuous Infusion 5-Fluorouracil and Cisplatin
LoRusso P, Pazdur R, Redman B, Kinzie J, Vaitkevicius V. Low-Dose Continuous Infusion 5-Fluorouracil and Cisplatin. American Journal Of Clinical Oncology 1989, 12: 486-490. PMID: 2686394, DOI: 10.1097/00000421-198912000-00005.Peer-Reviewed Original ResearchConceptsContinuous infusionLow-dose continuous infusionMedian performance statusHand-foot syndromeSubclavian vein thrombosisDose continuous infusionMeasurable diseaseMedian durationMedian survivalPartial responsePerformance statusVein thrombosisComplete responseMedian ageGastric ulcerationPatientsSingle agentAntineoplastic activityCisplatinMonthsRest periodInfusionTrialsSurvivalToxicity