2024
990O Final results from phase I, first-in-human, dose escalation study of a first-in-class anti-ILT2 antibody, SAR444881, alone and with pembrolizumab or cetuximab, in patients with advanced solid tumors
Perets R, Stemmer S, Geva R, Golan T, Fakih M, Cohen J, Lieu C, Jin Z, Lorusso P, Friedman I, Hakim M, Ziv D, Hashmueli S, Mandel I, Moshe T, Crawford N, Abbadessa G, Perez R, Wu M, Borad M. 990O Final results from phase I, first-in-human, dose escalation study of a first-in-class anti-ILT2 antibody, SAR444881, alone and with pembrolizumab or cetuximab, in patients with advanced solid tumors. Annals Of Oncology 2024, 35: s675. DOI: 10.1016/j.annonc.2024.08.1049.Peer-Reviewed Original ResearchThe HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results
Lewis G, Li G, Guo J, Yu S, Fields C, Lee G, Zhang D, Dragovich P, Pillow T, Wei B, Sadowsky J, Leipold D, Wilson T, Kamath A, Mamounas M, Lee M, Saad O, Choeurng V, Ungewickell A, Monemi S, Crocker L, Kalinsky K, Modi S, Jung K, Hamilton E, LoRusso P, Krop I, Schutten M, Commerford R, Sliwkowski M, Cho E. The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results. Nature Communications 2024, 15: 466. PMID: 38212321, PMCID: PMC10784567, DOI: 10.1038/s41467-023-44533-z.Peer-Reviewed Original ResearchConceptsHER2 antibody-drug conjugatesAntibody-drug conjugatesMetastatic breast cancerPhase 1 trialBreast cancerHER2-positive metastatic breast cancerHER2-positive breast cancerObjective response rateDose-escalation studyDuration of responseModel of HER2Anti-tumor activityMechanism of actionTrastuzumab deruxtecanPulmonary toxicityTrastuzumab emtansinePreclinical characterizationResponse rateHigh dosesVivo efficacySecondary objectiveEarly signsPotent cytotoxic agentCytotoxic agentsCancer
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 timeNCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors
Cecchini M, Walther Z, Wei W, Hafez N, Pilat M, Boerner S, Durecki D, Eder J, Schalper K, Chen A, LoRusso P. NCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors. Cancer Research Communications 2023, 3: 1113-1117. PMID: 37377610, PMCID: PMC10292219, DOI: 10.1158/2767-9764.crc-22-0485.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityHomologous recombination deficiencyPARP inhibitorsStable diseaseWeekly irinotecanObjective responseDay 1Day 3Solid tumorsPhase I dose-escalation studyTwice daily days 1I dose-escalation studyPhase I clinical trialDaily days 1Dose level 1Doses of veliparibGrade 3 neutropeniaMultiple-dose schedulesProgression-free survivalAdvanced solid tumorsDose-escalation studyEvaluable patientsNonoverlapping toxicitiesDose scheduleSystemic treatmentThe MDM2–p53 antagonist BI 907828 in patients with advanced or metastatic solid tumors: results of a phase Ia, first-in-human, dose-escalation study
LoRusso P, Yamamoto N, Patel M, Laurie S, Bauer T, Geng J, Davenport T, Teufel M, Li J, Lahmar M, Gounder M. The MDM2–p53 antagonist BI 907828 in patients with advanced or metastatic solid tumors: results of a phase Ia, first-in-human, dose-escalation study. Cancer Discovery 2023, 13: 1802-1813. PMID: 37269344, PMCID: PMC10401071, DOI: 10.1158/2159-8290.cd-23-0153.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsSolid tumorsDay 1Common treatment-related adverse eventsGrowth differentiation factor-15 levelsMDM2-p53 antagonistsManageable safety profileAdvanced solid tumorsDose-escalation studyDose-limiting toxicityMetastatic solid tumorsDose-dependent increaseIA/IBAdverse eventsSafety profilePreliminary efficacyDedifferentiated liposarcomaClinical investigationCommon gradePatientsRelated commentaryIssue featureTarget engagementAntitumor activityTumorsFirst-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 biopsiesG1-2A 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
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 studyA phase 1b, multicenter, dose-escalation study of subasumstat (TAK-981) in combination with pembrolizumab in patients (pts) with advanced solid tumors.
Goel S, Ulahannan S, Olszanski A, LoRusso P, Sanborn R, Sharma S, Emens L, Reilley M, Priego V, Li S, Wang B, Dong L, Sachsenmeier K, Gibbs J, Gharavi R, Martinez A, Proscurshim I, Fram R, Gomez-Pinillos A, Rasco D. A phase 1b, multicenter, dose-escalation study of subasumstat (TAK-981) in combination with pembrolizumab in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 2506-2506. DOI: 10.1200/jco.2022.40.16_suppl.2506.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsCheckpoint inhibitorsDay 1Anti-PD-1 checkpoint inhibitorsMicrosatellite stable colorectal cancerSynergistic tumor growth inhibitionDose-escalation partPhase 1b studyPhase 2 dosePre-treated NSCLCPromising anti-tumor activityRelapsed/refractoryT cell-dependent antitumor responseAdvanced solid tumorsDose-escalation studyActivation of CD8Dose-limiting toxicityNatural killer cellsCell lung cancerFavorable safety profilePhase 2 clinical developmentSyngeneic mouse modelDependent immune responsesType 1 interferonAnti-tumor activityPhase 1b study of the novel first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in combination with pembrolizumab in patients with immune checkpoint inhibitor (ICI)-relapsed and refractory solid malignancies and dose escalation update.
Muller C, Chaney M, Cohen J, Garyantes T, Lin J, LoRusso P, Mita A, Mita M, Natale C, Orloff M, Papadopoulos K, Patel S, Ahnert J. Phase 1b study of the novel first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in combination with pembrolizumab in patients with immune checkpoint inhibitor (ICI)-relapsed and refractory solid malignancies and dose escalation update. Journal Of Clinical Oncology 2022, 40: 2574-2574. DOI: 10.1200/jco.2022.40.16_suppl.2574.Peer-Reviewed Original ResearchG protein-coupled estrogen receptorFavorable safety profileStable diseaseLong-term benefitsHuman dose-escalation studyProtein-coupled estrogen receptorMetastatic uveal melanoma patientsEncouraging anti-tumor activityClinical benefit rateDose-escalation portionPhase 1b studyRefractory solid malignanciesImmune checkpoint inhibitorsObjective response rateDose-escalation studyMetastatic solid tumorsUveal melanoma patientsDuration of treatmentAnti-tumor activityEstrogen receptor agonistsSmall molecule agonistsCTCAE v5.0Evaluable patientsMeasurable diseaseRECIST v1.1
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 conjugatesA phase I dose-escalation study of the MDM2-p53 antagonist BI 907828 in patients (pts) with advanced solid tumors.
LoRusso P, Gounder M, Patel M, Yamamoto N, Bauer T, Laurie S, Grempler R, Davenport T, Geng J, Rohrbacher M, Lahmar M. A phase I dose-escalation study of the MDM2-p53 antagonist BI 907828 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2021, 39: 3016-3016. DOI: 10.1200/jco.2021.39.15_suppl.3016.Peer-Reviewed Original ResearchDose-limiting toxicityAdvanced solid tumorsArm AAdverse eventsArm BSolid tumorsDay 1Phase I dose-escalation studyExperienced dose-limiting toxicityNon-hematologic adverse eventsTreatment-related adverse eventsI dose-escalation studyAntitumor activityBiomarkers GDF-15Dose-escalation partGrade 3 nauseaManageable safety profileMDM2-p53 antagonistsPreliminary PK dataDose-escalation studyPatient-derived xenograftsClearance/FCycle 1Favorable PK propertiesLogistic regression modelsSafety 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 efficacyA phase 1 dose-escalation study of intravenously (IV) administered TAK-676, a novel STING agonist, alone and in combination with pembrolizumab in patients (pts) with advanced or metastatic solid tumors.
Falchook G, Luke J, Strauss J, Gao X, LoRusso P, VOON P, Li C, Shaw M, Gregory R, Horn K, Gibbs J, Lineberry N, Stumpo K, Malek K, Olszanski A. A phase 1 dose-escalation study of intravenously (IV) administered TAK-676, a novel STING agonist, alone and in combination with pembrolizumab in patients (pts) with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2021, 39: tps2670-tps2670. DOI: 10.1200/jco.2021.39.15_suppl.tps2670.Peer-Reviewed Original ResearchMetastatic solid tumorsCombination armCheckpoint inhibitorsSTING agonistsNovel STING agonistSolid tumorsDose escalationEastern Cooperative Oncology Group performance status 0Anti-programmed death ligand 1 therapyDay 1Phase 1 dose-escalation studyAnti-programmed death-1Death ligand 1 therapyPerformance status 0Phase 2 doseProinflammatory tumor environmentSolid Tumors (RECIST) v.Immune checkpoint inhibitorsDose-escalation studyResponse Evaluation CriteriaInnate immune cellsPreliminary antitumor activityStandard therapeutic optionAntitumor immune mechanismsImmuno-oncology therapies
2020
CX-2009, a CD166-directed probody drug conjugate (PDC): Results from the first-in-human study in patients (Pts) with advanced cancer including breast cancer (BC).
Boni V, Burris III H, Liu J, Spira A, Arkenau H, Fidler M, Rosen L, Sweis R, Uboha N, Sanborn R, O'Neil B, Harding J, LoRusso P, Weise A, Garcia-Corbacho J, Victoria I, Frye J, Li R, Stroh M, Meric-Bernstam F. CX-2009, a CD166-directed probody drug conjugate (PDC): Results from the first-in-human study in patients (Pts) with advanced cancer including breast cancer (BC). Journal Of Clinical Oncology 2020, 38: 526-526. DOI: 10.1200/jco.2020.38.15_suppl.526.Peer-Reviewed Original ResearchTreatment-related adverse eventsBreast cancerQ3w scheduleAdvanced cancerGrade 3 treatment-related adverse eventsHuman studiesCommon treatment-related adverse eventsMultiple solid tumor modelsInfusion-related reactionsPhase II doseAdvanced solid tumorsDose-escalation phaseDose-escalation studyPhase II expansionClinical trial informationPopulation pharmacokinetic simulationsMicrotubule inhibitorsSolid tumor modelsTumor-associated proteasesCX-072Prior therapyQ2W dosingQ3W dosingAdverse eventsPartial response
2019
A phase Ia/Ib, open label, multicenter, dose-escalation study of BI 907828 (MDM2-p53 antagonist) in adult patients with advanced or metastatic solid tumors.
Chong C, Bauer T, Laurie S, Patel M, Yamamoto N, Davenport T, Geng J, Gibson N, Vallaster M, LoRusso P. A phase Ia/Ib, open label, multicenter, dose-escalation study of BI 907828 (MDM2-p53 antagonist) in adult patients with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2019, 37: tps3166-tps3166. DOI: 10.1200/jco.2019.37.15_suppl.tps3166.Peer-Reviewed Original ResearchDose-limiting toxicityMetastatic solid tumorsFirst treatment cycleSolid tumorsEvaluable patientsPrimary endpointTreatment cyclesPhase 1bPreliminary anti-tumor activityMDM2-p53 antagonistsNon-squamous NSCLCDose-escalation studyDose-escalation trialSoft tissue sarcomasNumber of patientsTP53 wild-type statusWild-type statusAnti-tumor activityMDM2 amplification statusTumor protein 53New anti-cancer drugsIA/IBOpen labelRECIST v1.1Brain metastases
2017
A phase Ib dose escalation study of combined inhibition of IDO1 (GDC-0919) and PD-L1 (atezolizumab) in patients (pts) with locally advanced or metastatic solid tumors.
Burris H, Gordon M, Hellmann M, LoRusso P, Emens L, Hodi F, Lieu C, Infante J, Tsai F, Eder J, Cleary J, Jelovac D, Tsuhako A, Mueller L, Lin R, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis S. A phase Ib dose escalation study of combined inhibition of IDO1 (GDC-0919) and PD-L1 (atezolizumab) in patients (pts) with locally advanced or metastatic solid tumors. Journal Of Clinical Oncology 2017, 35: 105-105. DOI: 10.1200/jco.2017.35.15_suppl.105.Peer-Reviewed Original ResearchMetastatic solid tumorsPD-L1Phase Ib dose-escalation studySolid tumorsEffector T cell activityPrior systemic therapyDose-escalation studyT cell activityPreliminary efficacy dataHeterogeneous patient populationDose-dependent decreaseAnti-tumor activityCombination of GDCSelect tumor typesImmunogenic stateStable diseaseTumor pharmacodynamicsBID dosingExpansion cohortSepsis syndromeTreatment discontinuationEscalation studyPartial responsePlasma kynureninePrior immunotherapy
2013
Phase I, first-in-human, open-label, dose-escalation study of U3-1565, a fully human anti-HB-EGF monoclonal antibody, in patients with advanced solid tumors.
Moore K, Bendell J, Olszanski A, Desai M, Jansen M, Scheyer R, Senaldi G, LoRusso P. Phase I, first-in-human, open-label, dose-escalation study of U3-1565, a fully human anti-HB-EGF monoclonal antibody, in patients with advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2519-2519. DOI: 10.1200/jco.2013.31.15_suppl.2519.Peer-Reviewed Original ResearchAdvanced solid tumorsYear old femaleAnti-tumor activitySolid tumorsMonoclonal antibodiesDose level cohortsDose-expansion studyDose-escalation studyBi-exponential dispositionEpidermal growth factor-like growth factorEGF family membersTumor growth inhibitionFactor-like growth factorG1 toxicityProgressive diseaseAnti-angiogenesis activityStandard treatmentPatientsRelated AEsExtension phasePhase IGrowth factorLevel cohortsWeeksWeeklyPhase I, dose-escalation study of the investigational drug TAK-733, an oral MEK inhibitor, in patients (pts) with advanced solid tumors.
Adjei A, LoRusso P, Ribas A, Sosman J, Pavlick A, Dy G, Zhou X, Gangolli E, Walker R, Kneissl M, Faucette S, Neuwirth R, Bozon V. Phase I, dose-escalation study of the investigational drug TAK-733, an oral MEK inhibitor, in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2528-2528. DOI: 10.1200/jco.2013.31.15_suppl.2528.Peer-Reviewed Original ResearchAdvanced solid tumorsDrug-related AEsSolid tumorsAcneiform dermatitisTAK-733Creatine phosphokinase increaseECOG PS 0Oral MEK inhibitorDose-escalation studyDose-proportional mannerMean accumulation ratioPeripheral blood samplesAnti-tumor activitySteady-state exposurePower model analysisStable diseasePS 0Partial responseEvaluable tumorsPeripheral bloodPustular rashBlood samplesXenograft modelHuman studiesMaximal efficacy
2012
456P Multicenter, Dose-Escalation Study of the Investigational Drug Tak-733, An Oral Mek inhibitor, in Patients (PTS) with Advanced Solid Tumors: Preliminary Phase 1 Results
Adjei A, LoRusso P, Ribas A, Sosman J, Dy G, Chmielowski B, Lipman P, Zhou X, Gangolli E, Bozón V. 456P Multicenter, Dose-Escalation Study of the Investigational Drug Tak-733, An Oral Mek inhibitor, in Patients (PTS) with Advanced Solid Tumors: Preliminary Phase 1 Results. Annals Of Oncology 2012, 23: ix158. DOI: 10.1016/s0923-7534(20)33014-3.Peer-Reviewed Original ResearchDose-limiting toxicityDrug-related AEsAdvanced solid tumorsAnti-tumor activityTAK-733Solid tumorsECOG PS 0Oral MEK inhibitorDose-escalation studyMedian age 58Non-hematologic malignanciesPeripheral blood lymphocytesCycle 1Multiple xenograft modelsEvaluable ptsStable diseasePartial responsePS 0Dose escalationEvaluable tumorsAdvisory BoardBlood lymphocytesAge 58Blood samplesXenograft model