2024
Phase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors.
Falchook G, LoRusso P, Goldman J, El-Khoueiry A, Tolcher A, Xing Y, Henry J, Keam B, Kim D, Kim T, Kim H, Hong M, Kim M, Lee D, Lee S, Jeon J, Hayslip J, Xu C, Garon E. Phase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors. Journal Of Clinical Oncology 2024, 42: 2529-2529. DOI: 10.1200/jco.2024.42.16_suppl.2529.Peer-Reviewed Original ResearchTreatment related adverse eventsClinical benefit rateOverall response ratePD-L1Dose levelsPD-(L)1Complete responsePartial responseSolid tumorsHead and neck squamous cellAntibody targeting PD-L1Treated with checkpoint inhibitorsActivation of T cellsDose-limiting toxicityPre-treated patientsPD-(L)1 inhibitorsDose-expansion cohortRelapsed/refractory solid tumorsWeight-based dosingLines of treatmentPD-L1 antagonistsRelated adverse eventsAnti-tumor effectsDose-dependent increaseMultiple tumor types
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
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
Phase 1 Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844)
Roussos Torres ET, Rafie C, Wang C, Lim D, Brufsky A, LoRusso P, Eder JP, Chung V, Downs M, Geare M, Piekarz R, Streicher H, Anforth L, Rudek MA, Zhu Q, Besharati S, Cimino-Mathews A, Anders RA, Stearns V, Jaffee EM, Connolly RM. Phase 1 Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844). Clinical Cancer Research 2021, 27: clincanres.5017.2021. PMID: 34135021, PMCID: PMC8563383, DOI: 10.1158/1078-0432.ccr-20-5017.Peer-Reviewed Original ResearchConceptsCD8/FOXP3 ratioAdvanced solid tumorsAdverse eventsAddition of ICIFOXP3 ratioSolid tumorsGrade 3/4 adverse eventsRegulatory T cell ratioTreatment-related adverse eventsImmune checkpoint inhibitor efficacyTriple-negative breast cancerMulticenter phase I clinical trialPhase I clinical trialObjective response ratePhase II doseT cell ratioCheckpoint inhibitor efficacyPhase 1 studyCombination of entinostatHistone deacetylase inhibitor entinostatRECIST 1.1Primary endpointSecondary endpointsComplete responseDose escalation
2020
Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies
Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clinical Cancer Research 2020, 26: 1247-1257. PMID: 31527168, PMCID: PMC7528620, DOI: 10.1158/1078-0432.ccr-18-4071.Peer-Reviewed Original ResearchConceptsAdvanced malignanciesGrade treatment-related adverse eventsTreatment-related adverse eventsAdequate organ functionHigh interpatient variabilityFavorable PK profileOptimal dosing schemePrimary endpointAdverse eventsOral clearancePartial responseComplete responsePhase 1/2Terminal eliminationTolerability studyPatient populationPharmacodynamic profileInterpatient variabilityDosing schemesDistinct pharmacokineticsTherapeutic indexOrgan functionPK profilesExtraterminal (BET) inhibitorsTarget inhibition
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
2015
Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer.
Kwak E, LoRusso P, Hamid O, Janku F, Kittaneh M, Catenacci D, Chan E, Bekaii-Saab T, Amore B, Hwang Y, Tang R, Ngarmchamnanrith G, Hong D. Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer. Journal Of Clinical Oncology 2015, 33: 1-1. DOI: 10.1200/jco.2015.33.3_suppl.1.Peer-Reviewed Original ResearchAMG 337MET kinase inhibitorGastroesophageal junctionGI cancersClinical activityCommon treatment-emergent AEsKinase inhibitorsAdequate organ functionDose-expansion phaseSubset of ptsTreatment-emergent AEsAdvanced solid tumorsDose-limiting toxicityKey eligibility criteriaAmplification/mutationMeasurable diseaseAdult patientsComplete responsePartial responseDose escalationMedian ageGI tumorsAE profileEsophageal cancerMET pathway
2007
AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, in combination with chemotherapy in adult patients with advanced solid tumors
Mita A, Wang D, Takimoto C, Malseed E, Nguyen L, Rasmussen E, Storgard C, LoRusso P. AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, in combination with chemotherapy in adult patients with advanced solid tumors. Journal Of Clinical Oncology 2007, 25: 14033-14033. DOI: 10.1200/jco.2007.25.18_suppl.14033.Peer-Reviewed Original ResearchDose-limiting toxicityAMG 386Advanced solid tumorsComplete responsePK profilesAdult patientsSolid tumorsMedian age 59.5 yearsAntitumor activityOpen-label studyGemcitabine/cisplatinFurther clinical studiesFormation of antibodiesTumor response dataSerious AEsCancer refractoryFOLFOX-4Stable diseaseProgressive diseaseWeekly administrationTumor responseWeek 16Bladder cancerDisease progressionWeek 8
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