2024
First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors
Shimizu T, Powderly J, Razak A, LoRusso P, Miller K, Kao S, Kongpachith S, Tribouley C, Graham M, Stoll B, Patel M, Sahtout M, Blaney M, Leibman R, Golan T, Tolcher A. First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors. Frontiers In Oncology 2024, 14: 1376551. PMID: 39534099, PMCID: PMC11555770, DOI: 10.3389/fonc.2024.1376551.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-escalation phaseDose escalationSolid tumorsSurface of regulatory T cellsRecommended phase 2 doseSuppress antitumor immune responsesCombination therapy cohortsDose-proportional PKMonotherapy-treated patientsPhase 2 doseMedian response durationAntitumor immune responseDose-limiting toxicityTherapy-treated patientsRegulatory T cellsMaximum administered doseFirst-in-humanDose escalation resultsGlycoprotein A repetitionsPromote tumor growthBlood biomarker dataDose expansionPretreated patientsEscalating doses
2021
A phase 1b, open-label, dose-escalation study to evaluate camidanlumab tesirine (Cami) as monotherapy in patients (pts) with advanced solid tumors.
Puzanov I, LoRusso P, Papadopoulos K, Chen C, LeBruchec Y, He X, Cousin T, Havenith K, Boni J, Bendell J. A phase 1b, open-label, dose-escalation study to evaluate camidanlumab tesirine (Cami) as monotherapy in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2021, 39: 2556-2556. DOI: 10.1200/jco.2021.39.15_suppl.2556.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAdvanced solid tumorsDisease control rateSolid tumorsDose escalationGrade treatment-emergent adverse eventsNon-small cell lung cancerTumor-specific immune responsesTriple-negative breast cancerDose-escalation partPhase 2 dosePrior systemic therapyAntitumor activityMedian treatment durationOpen-label studyDose-escalation studyPhase 1b trialPrimary tumor typeRegulatory T cellsCell lung cancerPreliminary antitumor activityPK/PD dataRenal cell carcinomaSolid tumor modelsAntibody-drug conjugates
2020
Phase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer.
Powderly J, Chmielowski B, Brahmer J, Piha-Paul S, Bowyer S, LoRusso P, Catenacci D, Wu C, Barve M, Chisamore M, Nasrah N, Johnson D, Ho W. Phase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer. Journal Of Clinical Oncology 2020, 38: tps3163-tps3163. DOI: 10.1200/jco.2020.38.15_suppl.tps3163.Peer-Reviewed Original ResearchCheckpoint inhibitorsExpansion cohortT cellsPhase 1 dose escalationAnti-tumor immune responseTumor microenvironmentPhase I/IIPreliminary anti-tumor activityCohort expansion phaseCohort expansion studyPhase 2 dosePredominant chemokine receptorPhase 1/2 studyDose-escalation phaseEffector T cellsRegulatory T cellsAnti-tumor responseTumor-associated macrophagesAnti-tumor efficacyAnti-tumor activityEligible subjectsDendritic cellsDose escalationPhase 1/2Advanced cancer
2019
Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors
Jung KH, LoRusso P, Burris H, Gordon M, Bang YJ, Hellmann MD, Cervantes A, de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott D, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis SL. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clinical Cancer Research 2019, 25: 3220-3228. PMID: 30770348, PMCID: PMC7980952, DOI: 10.1158/1078-0432.ccr-18-2740.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorHumansImidazolesIndoleamine-Pyrrole 2,3,-DioxygenaseIndolesMagnetic Resonance ImagingMiddle AgedNeoplasm MetastasisNeoplasm StagingNeoplasmsTomography, X-Ray ComputedTreatment OutcomeConceptsPD-L1 inhibitorsT cellsPartial responseAdvanced cancerDay 1Dose levelsCommon treatment-related AEsDose-escalation stageTreatment-related AEsAdvanced solid tumorsEffector T cellsRegulatory T cellsLinear pharmacokinetic profileLocal tumor microenvironmentInvestigational small-molecule inhibitorExpansion patientsKynurenine accumulationComplete responseImmune suppressionIntravenous infusionAcceptable safetyTryptophan depletionNavoximodAtezolizumabPlasma Kyn
2017
Dose escalation results from a first-in-human, phase 1 study of the glucocorticoid-induced TNF receptor-related protein (GITR) agonist AMG 228 in patients (Pts) with advanced solid tumors.
Tran B, Carvajal R, Marabelle A, Patel S, LoRusso P, Rasmussen E, Juan G, Upreti V, Ngarmchamnanrith G, Schöffski P. Dose escalation results from a first-in-human, phase 1 study of the glucocorticoid-induced TNF receptor-related protein (GITR) agonist AMG 228 in patients (Pts) with advanced solid tumors. Journal Of Clinical Oncology 2017, 35: 2521-2521. DOI: 10.1200/jco.2017.35.15_suppl.2521.Peer-Reviewed Original ResearchGlucocorticoid-induced TNF receptor-related proteinAdvanced solid tumorsDose-limiting toxicityPhase 1 studyAdverse eventsSolid tumorsObjective responseDose escalationCell carcinomaNon-small cell lung cancerRefractory advanced colorectal cancerTreatment-emergent adverse eventsHuman IgG1 monoclonal antibodyPhase 2 doseUrothelial transitional cell carcinomaAdvanced colorectal cancerRegulatory T cellsCell lung cancerSquamous cell carcinomaTransitional cell carcinomaDose-escalation resultsT cell activationReceptor-related proteinPopulation of ptsIgG1 monoclonal antibody