2024
Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial
Roussos Torres E, Ho W, Danilova L, Tandurella J, Leatherman J, Rafie C, Wang C, Brufsky A, LoRusso P, Chung V, Yuan Y, Downs M, O’Connor A, Shin S, Hernandez A, Engle E, Piekarz R, Streicher H, Talebi Z, Rudek M, Zhu Q, Anders R, Cimino-Mathews A, Fertig E, Jaffee E, Stearns V, Connolly R. Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial. Nature Cancer 2024, 5: 866-879. PMID: 38355777, PMCID: PMC11552660, DOI: 10.1038/s43018-024-00729-w.Peer-Reviewed Original ResearchHormone receptor-positive breast cancerReceptor-positive breast cancerTriple-negative breast cancerClinical benefit rateProgression-free survivalBreast cancerBenefit rateAdvanced HER2-negative breast cancerAdvanced triple-negative breast cancerHER2-negative breast cancerResponse rateNivolumab + ipilimumabPD-L1 statusDose-limiting toxicityPhase Ib trialTumor mutational burdenPhase II trialDose escalationExpansion cohortPD-L1II trialMutational burdenPrimary endpointSecondary endpointsMyeloid cells
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
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 escalationA 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 duration
2020
A phase I study of CD40 agonist ABBV-927 plus OX40 agonist ABBV-368 with or without the PD-1 inhibitor budigalimab in patients with advanced solid tumors.
Powderly J, Tolcher A, LoRusso P, Blaney M, Dacosta D, Henner W, McDevitt M, Miller K, Golan T. A phase I study of CD40 agonist ABBV-927 plus OX40 agonist ABBV-368 with or without the PD-1 inhibitor budigalimab in patients with advanced solid tumors. Journal Of Clinical Oncology 2020, 38: tps3147-tps3147. DOI: 10.1200/jco.2020.38.15_suppl.tps3147.Peer-Reviewed Original ResearchNon-small cell lung cancerTriple-negative breast cancerAdvanced solid tumorsDisease-specific cohortsSolid tumorsCostimulatory moleculesEastern Cooperative Oncology Group performance statusCentral nervous system metastasesPD-ligand 1 (PD-L1) inhibitorsRegulatory T cell activityNascent immune responsesPhase 2 doseNervous system metastasesProgression-free survivalPhase 1 studyT cell activityCell lung cancerDuration of responseOverall response ratePlatinum-based therapyKey costimulatory moleculesT cell activationAdaptive immune systemPrimary endpointSecondary endpoints
2019
Phase 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
2013
Trastuzumab emtansine (T-DM1) in previously treated HER2-positive metastatic breast cancer (MBC): Results from an expanded access study.
Yardley D, Krop I, LoRusso P, Robert N, Mayer M, Abidoye O, Lai C, Yoo B, Perez E. Trastuzumab emtansine (T-DM1) in previously treated HER2-positive metastatic breast cancer (MBC): Results from an expanded access study. Journal Of Clinical Oncology 2013, 31: 166-166. DOI: 10.1200/jco.2013.31.26_suppl.166.Peer-Reviewed Original ResearchMetastatic breast cancerObjective response rateHER2-positive metastatic breast cancerT-DM1Investigator-assessed objective response rateMedian cumulative anthracycline doseAccess StudyCumulative anthracycline doseCytotoxic agent DM1HER2-directed agentsMost common gradeUS multicenter studyNew safety signalsRate of gradeConventional clinical trialsAnthracycline doseGrade AEsMBC therapyMeasurable diseaseMedian LVEFPrior anthracyclineSecondary endpointsMUGA scanCardiac dysfunctionMulticenter studyA phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC).
Goncalves P, Kummar S, Siu L, Hansen A, Savvides P, Sukari A, Chao J, Heilbrun L, Pilat M, Smith D, Casetta L, Boerner S, LoRusso P. A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC). Journal Of Clinical Oncology 2013, 31: 6045-6045. DOI: 10.1200/jco.2013.31.15_suppl.6045.Peer-Reviewed Original ResearchProgression-free survivalAdenoid cystic carcinomaSuberoylanilide hydroxamic acidMetastatic adenoid cystic carcinomaOverall survivalAdverse eventsResponse durationResponse rateEvaluable patientsOnly grade 3 adverse eventGrade 3 adverse eventsMedian progression-free survivalTreatment of ACCAdequate organ functionMedian overall survivalPhase II studyPhase II trialHistone deacetylasesDrug combination studiesChemo-naïveChemotherapy regimensII trialOral painSecondary endpointsThromboembolic events
2012
A phase I study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced, HER2-positive (HER2+) breast cancer.
Munster P, Miller K, Krop I, Dhindsa N, Reynolds J, Geretti E, Niyikiza C, Nielsen U, Hendriks B, Wickham T, Moyo V, LoRusso P. A phase I study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced, HER2-positive (HER2+) breast cancer. Journal Of Clinical Oncology 2012, 30: tps663-tps663. DOI: 10.1200/jco.2012.30.15_suppl.tps663.Peer-Reviewed Original ResearchAdvanced breast cancerMaximum feasible doseBreast cancerMM-302Liposomal doxorubicinHER2-positive breast cancerTumor cellsAdequate performance statusAnthracycline-free regimensBone marrow reserveDose-escalation portionClinical benefit rateDose-limiting toxicityDose-escalation designHER2-positive cancersPreliminary efficacy dataHuman phase IStandard therapy existsBreast cancer therapyAvailable anthracyclinesPrimary endpointSecondary endpointsMarrow reservePerformance statusStandard therapy
2009
Tremelimumab in combination with exemestane as novel immunotherapy for patients with advanced breast cancer
Vonderheide R, LoRusso P, Khalil M, Heath E, Khaira D, Soulieres D, Dorazio P, Mariani G, Usari T, Domchek S. Tremelimumab in combination with exemestane as novel immunotherapy for patients with advanced breast cancer. Journal Of Clinical Oncology 2009, 27: 3034-3034. DOI: 10.1200/jco.2009.27.15_suppl.3034.Peer-Reviewed Original ResearchBreast cancerHormone receptor breast cancerAnti-CTLA4 monoclonal antibodySingle-agent doseUnknown receptor statusCycles of therapyPhase II doseSingle-agent antitumor activityAdvanced breast cancerDose-escalation trialSerum transaminase elevationTumor response evaluationCycle 1Assessment of safetyStable diseaseAdvanced diseasePrimary endpointSecondary endpointsTransaminase elevationAutoimmune thyroiditisHormone replacementNovel immunotherapiesObjective responsePharmacokinetic interactionsReceptor status