2024
Circulating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors
Hu Y, Narayan A, Xu Y, Wolfe J, Vu D, Trinh T, Kantak C, Ivy S, Eder J, Deng Y, LoRusso P, Kim J, Patel A. Circulating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors. JCO Precision Oncology 2024, 8: e2300289. PMID: 38412387, PMCID: PMC10914240, DOI: 10.1200/po.23.00289.Peer-Reviewed Original ResearchConceptsCell-free circulating tumor DNANon-small-cell lung cancerSmall-cell lung cancerTriple-negative breast cancerPancreatic ductal adenocarcinomaAdvanced solid tumorsVariant allele fractionRadiographic responseOverall survivalCombination therapySolid tumorsCtDNA levelsLung cancerPretreated advanced solid tumorsDays of combination therapyMetastatic pancreatic ductal adenocarcinomaResponse to anticancer therapyAssociated with disease progressionProgression-free survivalPlasma samplesLead-inPoly(ADP-riboseInferior OSTumor DNASurvival outcomesEntinostat, 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 1a dose-escalation study of PY159, a monoclonal antibody targeting TREM1 (triggering receptor expressed on myeloid cells 1).
Winer I, Patnaik A, Barve M, Kummar S, Schenk E, LoRusso P, Yeku O, Fu S, Jahchan N, Myers M, Liang L, Deegan D, Jackson L, Li Y, Reyno L, Chamberlain M. A phase 1a dose-escalation study of PY159, a monoclonal antibody targeting TREM1 (triggering receptor expressed on myeloid cells 1). Journal Of Clinical Oncology 2023, 41: 2523-2523. DOI: 10.1200/jco.2023.41.16_suppl.2523.Peer-Reviewed Original ResearchSingle agentDose levelsNon-small cell lung cancerAdvanced refractory solid tumorsDose-escalation study designImmune-related adverse eventsTriple-negative breast cancerImmune checkpoint inhibitorsAcceptable safety profileDose-escalation studyRefractory solid tumorsCell lung cancerArchival tumor tissueEnrollment of subjectsImmune-related reactionsDose proportionalECOG PSRECIST 1.1Stable diseaseTREM1 expressionCheckpoint inhibitorsAdverse eventsPartial responseRadiographic responseGynecologic cancer
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 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
412 First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors
Garralda E, Geva R, Ben-Ami E, Maurice-Dror C, Calvo E, LoRusso P, Türeci Ö, Niewood M, Şahin U, Jure-Kunkel M, Forssmann U, Ahmadi T, Melero I. 412 First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors. Journal For ImmunoTherapy Of Cancer 2020, 8: a250-a251. DOI: 10.1136/jitc-2020-sitc2020.0412.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-limiting toxicityPhase I/IIa trialTransaminase elevationAdverse eventsSolid tumorsIIa trialClinical activityT cellsDose levelsGrade 3 transaminase elevationTreatment-related adverse eventsEffector memory T cellsSerum interferon-gamma levelTriple-negative breast cancerInitial clinical activityAntitumor activityImmune checkpoint inhibitorsManageable safety profilePD-L1 axisInterferon-gamma levelsMemory T cellsEarly clinical activityEnd of infusionNarrow therapeutic windowA 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
CX-072, a PD-L1 Probody therapeutic, as monotherapy in patients with advanced solid tumors: Preliminary results of PROCLAIM-CX-072.
Naing A, Thistlethwaite F, Spira A, Garcia-Corbacho J, Randhawa M, Eskens F, O'Neil B, Lavernia J, Uboha N, Hamid O, El-Khoueiry A, Benson B, Garner W, Huels V, Arkenau H, LoRusso P. CX-072, a PD-L1 Probody therapeutic, as monotherapy in patients with advanced solid tumors: Preliminary results of PROCLAIM-CX-072. Journal Of Clinical Oncology 2019, 37: 2513-2513. DOI: 10.1200/jco.2019.37.15_suppl.2513.Peer-Reviewed Original ResearchCutaneous squamous cell carcinomaSquamous cell carcinomaSmall bowel adenocarcinomaCX-072Advanced solid tumorsAdverse eventsSolid tumorsPD-L1Cell carcinomaSkin lesionsAnti-programmed cell death ligand-1 (PD-L1) immunotherapiesGrade 3/4 treatment-related adverse eventsAnal squamous cell carcinomaDeath ligand 1 (PD-L1) immunotherapyStandard curative treatment optionsTreatment-related adverse eventsTriple-negative breast cancerAnti-CTLA4 treatmentPhase 1/2a studyMedian treatment durationCurative treatment optionPD-L1 expressionUnresectable solid tumorsPrior regimensBowel adenocarcinoma
2015
Phase I dose-finding study of the gamma secretase inhibitor PF-03084014 (PF-4014) in combination with docetaxel in patients (pts) with advanced triple-negative breast cancer (TNBC).
Curigliano G, Aftimos P, Dees E, LoRusso P, Pegram M, Awada A, Huang B, Cesari R, Jiang Y, Shaik M, Kern K, Locatelli M. Phase I dose-finding study of the gamma secretase inhibitor PF-03084014 (PF-4014) in combination with docetaxel in patients (pts) with advanced triple-negative breast cancer (TNBC). Journal Of Clinical Oncology 2015, 33: 1068-1068. DOI: 10.1200/jco.2015.33.15_suppl.1068.Peer-Reviewed Original Research
2010
189 Preclinical activity of the poly (ADP-ribose) polymerase (PARP) inhibitor ABT-888 in combination with irinotecan in ovarian and triple negative breast cancers
Nechiporchik N, Lieb K, Marquette L, Polin L, Peters G, Chen A, Ethier S, LoRusso P, Burger A. 189 Preclinical activity of the poly (ADP-ribose) polymerase (PARP) inhibitor ABT-888 in combination with irinotecan in ovarian and triple negative breast cancers. European Journal Of Cancer Supplements 2010, 8: 64. DOI: 10.1016/s1359-6349(10)71894-2.Peer-Reviewed Original ResearchTriple-negative breast cancerNegative breast cancerPolymerase inhibitor ABT-888Preclinical activityBreast cancerABT-888IrinotecanCancer