2023
First-in-human phase 1 dose escalation study of the KAT6 inhibitor PF-07248144 in patients with advanced solid tumors.
Sommerhalder D, Hamilton E, Mukohara T, Yonemori K, Mita M, Yamashita T, Zheng J, Liu L, Maity A, Homji Mishra N, Bogg O, Li M, LoRusso P. First-in-human phase 1 dose escalation study of the KAT6 inhibitor PF-07248144 in patients with advanced solid tumors. Journal Of Clinical Oncology 2023, 41: 1054-1054. DOI: 10.1200/jco.2023.41.16_suppl.1054.Peer-Reviewed Original ResearchWhite blood cellsEndocrine therapyPartial responsePart 1BPhase 1 dose-escalation studyHuman phase 1 studyPreclinical anti-tumor activityDurable partial responseTreatment-related AEsAdvanced solid tumorsDose-escalation studySystemic anticancer therapyPhase 1 studyAnti-tumor activityPart 1AEscalation studyMedian agePrior linesStandard therapyDose escalationCDK4/6 inhibitorsDisease progressionBreast cancerTumor biopsiesG1-2
2022
Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma.
Fanucci K, Pilat M, Shah R, Boerner S, Li J, Durecki D, Drappatz J, Collichio F, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Bao X, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma. Journal Of Clinical Oncology 2022, 40: 2035-2035. DOI: 10.1200/jco.2022.40.16_suppl.2035.Peer-Reviewed Original ResearchProgression-free survivalMedian progression-free survivalStable diseaseDuration of responseOverall response ratePARP inhibitorsOverall survivalStandard therapyOlaparib monotherapyMulticenter phase 2 trialCDKN2A deletionClinical predictive markersGrade 3 lymphopeniaProlonged stable diseasePhase 2 trialGrade 4 tumorsFuture patient stratificationRecent preclinical studiesHigh-grade gliomasNovel drug combinationsContrast-enhancing gliomasEligible ptsEvaluable ptsRecent histologyPrimary endpoint
2021
Safety and preliminary efficacy from the phase 1 portion of MasterKey-01: A First-in-human dose-escalation study to determine the recommended phase 2 dose (RP2D), pharmacokinetics (PK) and preliminary antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients (pts) with advanced solid malignancies.
Schram A, Ahnert J, Patel M, Jauhari S, Sachdev J, Zhu V, LoRusso P, Nguyen D, Le X, O'Connor M, Waters N, Cook C, Witt K, Humphrey R, Janne P, Hamilton E. Safety and preliminary efficacy from the phase 1 portion of MasterKey-01: A First-in-human dose-escalation study to determine the recommended phase 2 dose (RP2D), pharmacokinetics (PK) and preliminary antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients (pts) with advanced solid malignancies. Journal Of Clinical Oncology 2021, 39: 3086-3086. DOI: 10.1200/jco.2021.39.15_suppl.3086.Peer-Reviewed Original ResearchFE cohortHER2 amplificationSolid tumorsHuman dose-escalation studyDose-escalation cohortsManageable safety profilePhase 2 doseAdvanced solid malignanciesAdvanced solid tumorsDose-escalation studyMetastatic solid tumorsPreliminary antitumor activityPhase 1 portionAnti-tumor activityTumor growth inhibitionBID cohortQD scheduleEGFR/HER2Adverse eventsEscalation cohortsPartial responseProgressive diseaseStandard therapySafety profilePreliminary efficacy
2020
Masterkey-01: Phase I/II, open-label multicenter study to assess safety, tolerability, pharmacokinetics, and antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies.
Hamilton E, Patel M, Rodon J, Hong D, Schram A, Janne P, LoRusso P, Sachdev J, Ou S, Buck E, O'Connor M, Waters N, Witt K, Cook C. Masterkey-01: Phase I/II, open-label multicenter study to assess safety, tolerability, pharmacokinetics, and antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies. Journal Of Clinical Oncology 2020, 38: tps3665-tps3665. DOI: 10.1200/jco.2020.38.15_suppl.tps3665.Peer-Reviewed Original ResearchAntitumor activityStandard therapyPreliminary efficacyERBB mutationsOpen-label multicenter studySignificant unmet need existsPhase I/IIHER2 tyrosine kinase inhibitorPhase 2 doseAdvanced solid malignanciesAdequate drug exposureMetastatic solid tumorsPreliminary antitumor activityExon 20 insertionsOncogenic driver mutationsTyrosine kinase inhibitorsUnmet need existsAssessment of safetyCurrent eGFRExpansion cohortMulticenter studyPharmacodynamic effectsSolid malignanciesDrug exposureCohort 1
2019
466P Interim results from trial of SL-801, a novel XPO-1 inhibitor, in patients with advanced solid tumours
Wang J, Barve M, Chiorean E, LoRusso P, Courtney K, Qi D, Bullington J, Sardone M, Chen J, Brooks C, Shemesh S, Bauer T. 466P Interim results from trial of SL-801, a novel XPO-1 inhibitor, in patients with advanced solid tumours. Annals Of Oncology 2019, 30: v175. DOI: 10.1093/annonc/mdz244.028.Peer-Reviewed Original ResearchSchedule ADay 1Optimal dose/schedulePreliminary anti-tumor activityDose-escalation stageStudy dose levelsMetastatic solid tumorsDose/scheduleAggressive tumor behaviorAnti-tumor activityAssess pharmacokineticsStarting doseDose intensityStandard therapyPoor prognosisHematologic malignanciesTumor behaviorDose levelsSolid tumorsPatientsNuclear export proteinVivo activityDoseLonger recovery timeDaysA phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers.
Mobasher M, Miller R, Kwei L, Strahs D, Das V, Luciano G, Powderly J, Merchan J, Barve M, LoRusso P, Tripathi A, Luke J. A phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers. Journal Of Clinical Oncology 2019, 37: tps2646-tps2646. DOI: 10.1200/jco.2019.37.15_suppl.tps2646.Peer-Reviewed Original ResearchSingle agentCD73 antibodyTumor growthNon-small cell lungAdequate organ functionAnti-CD73 antibodiesOpen-label trialTreatment of patientsRenal cell carcinomaSelective A2AR antagonistNumber of malignanciesKnockout mice exhibitTriple-negative breastEligible patientsMeasurable diseaseLabel trialAdult patientsStandard therapyAdvanced cancerCD73 expressionImmunosuppressive adenosineMulticenter studyUrothelial bladderCell carcinomaCell lung
2017
Phase I study combining the aurora kinase A (AURKA) inhibitor alisertib (Ali) with mFOLFOX in gastrointestinal (GI) cancer.
Goff L, Azad N, Stein S, Whisenant J, Vaishampayan U, Hochster H, Connolly R, Weise A, LoRusso P, El-Rifai W, Berlin J. Phase I study combining the aurora kinase A (AURKA) inhibitor alisertib (Ali) with mFOLFOX in gastrointestinal (GI) cancer. Journal Of Clinical Oncology 2017, 35: 2593-2593. DOI: 10.1200/jco.2017.35.15_suppl.2593.Peer-Reviewed Original ResearchGI cancersStandard platinum-based therapyCorrelative biomarker studyDisease control rateMost frequent toxicitiesPreliminary clinical activityPlatinum-based therapyMajority of ptsEvaluable ptsStable diseaseEligible patientsFrequent toxicitiesHematologic toxicityPartial responseStandard therapyDose escalationInhibition of AURKAControl rateGastrointestinal cancerPreclinical dataClinical activityPlatinum agentsDose levelsInhibitor alisertibOptimal timing window
2015
Phase II study evaluating the effect of concomitant ramucirumab (RAM) on the pharmacokinetics (PK) of irinotecan (IRI) and its metabolite SN-38 when coadministered with folinic acid (FA) and 5-fluorouracil (5-FU) (FOLFIRI) in patients (pts) with advanced malignant solid tumors.
Wang D, Braiteh F, Lee J, Denlinger C, Shepard D, Chaudhary A, Lin Y, Gao L, Asakiewicz C, Nasroulah F, LoRusso P. Phase II study evaluating the effect of concomitant ramucirumab (RAM) on the pharmacokinetics (PK) of irinotecan (IRI) and its metabolite SN-38 when coadministered with folinic acid (FA) and 5-fluorouracil (5-FU) (FOLFIRI) in patients (pts) with advanced malignant solid tumors. Journal Of Clinical Oncology 2015, 33: 691-691. DOI: 10.1200/jco.2015.33.3_suppl.691.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAdvanced malignant solid tumorsPharmacokinetics of irinotecanMalignant solid tumorsMetabolite SN-38Folinic acidSN-38Safety populationStandard therapyEastern Cooperative Oncology Group performance statusSolid tumorsCycle 1Maximum observed drug concentrationFatigue/astheniaPhase II studyKey eligibility criteriaDose-normalized areaNew safety concernsC maxII studyPerformance statusAdverse eventsStudy treatmentIntravenous infusionPlasma concentrations
2012
507 Phase I, Open-Label, Randomized, Crossover Study Evaluating the Effects of Linifanib on Qtc Intervals in Patients with Solid Tumors
Chiu Y, LoRusso P, Ricker J, Li X, Pradhan R, Carlson D. 507 Phase I, Open-Label, Randomized, Crossover Study Evaluating the Effects of Linifanib on Qtc Intervals in Patients with Solid Tumors. Annals Of Oncology 2012, 23: ix173. DOI: 10.1016/s0923-7534(20)33069-6.Peer-Reviewed Original ResearchAdvanced solid tumorsDay 1Solid tumorsCardiac repolarizationAdequate organ functionECOG PS 0Primary end pointExposure-response analysisEffects modelMeasurable diseaseMorning doseOpen labelCrossover fashionPS 0QTc prolongationStandard therapyCrossover studyQTc intervalBaseline QTcFQTcF intervalStudy completionA 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
Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors
Demetri G, Russo P, MacPherson I, Wang D, Morgan J, Brunton V, Paliwal P, Agrawal S, Voi M, Evans T. Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors. Clinical Cancer Research 2009, 15: 6232-6240. PMID: 19789325, DOI: 10.1158/1078-0432.ccr-09-0224.Peer-Reviewed Original ResearchConceptsDose-limiting toxicitySolid tumorsHematologic toxicityFrequent treatment-related toxicitiesDurable stable diseaseGrade 2 proteinuriaGrade 2 rashGrade 3 fatigueGrade 3 hypocalcemiaGrade 3 lethargyGrade 3 nauseaI Dose-EscalationLess hematologic toxicityGrade 3 rashObjective tumor responsePhase II doseTreatment-related toxicityAdvanced solid tumorsDose-escalation studyMetastatic solid tumorsStandard therapy existsNontreatment daysStable diseaseDaily dosingStandard therapy