2024
Unlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates.
Ascione L, Guidi L, Prakash A, Trapani D, LoRusso P, Lou E, Curigliano G. Unlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates. American Society Of Clinical Oncology Educational Book 2024, 44: e431766. PMID: 38828973, DOI: 10.1200/edbk_431766.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesTumor sitePredictive biomarkersAntigen expressionLack of robust predictive biomarkersSelection of targeted therapiesRobust predictive biomarkersTarget antigen expressionTumor antigen expressionCancer treatment landscapeBiomarkers of responseImprove patient selectionTumor intrinsic featuresBiomarkers of safetyUnique adverse eventsIdentification of patientsPopulation of patientsClinically actionable biomarkersSmall-molecule agentsPatient-centred outcomesTreatment landscapeBiomarker-drivenTreatment resistanceClinical benefitPatient selectionThe 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
CBX-12-101: A first-in-human study of CBX-12, an alphalex peptide drug conjugate (PDC) in patients (pts) with advanced or metastatic solid tumors.
Rodriguez Rivera I, Hafez N, Tolcher A, LoRusso P, Wilks S, Tripathy D, Gara M, Pearson P, DeCillis A, Meric-Bernstam F. CBX-12-101: A first-in-human study of CBX-12, an alphalex peptide drug conjugate (PDC) in patients (pts) with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2023, 41: 3087-3087. DOI: 10.1200/jco.2023.41.16_suppl.3087.Peer-Reviewed Original ResearchTreatment-related AEsOvarian cancerBreast cancerFrequent treatment-related AEsHER2-negative breast cancerPlatinum-resistant ovarian cancerDaily x 3Daily x 5Hormone receptor positiveSingle-agent antitumor activityMetastatic solid tumorsPhase 1 trialAnti-drug antibodiesNegative breast cancerAnti-tumor activityAntibody-drug conjugatesFebrile neutropeniaRECIST v1.1WBC decreaseExpansion cohortFIH studiesPlasma PKTumor cell membranesHuman studiesSolid tumors
2022
Phase 1 study of SGN-ALPV, a novel, investigational vedotin antibody–drug conjugate directed to ALPP/ALPPL2 in advanced solid tumors (SGNALPV-001, trial in progress).
Lakhani N, Friedman C, Perez C, Wehr A, McGoldrick S, LoRusso P. Phase 1 study of SGN-ALPV, a novel, investigational vedotin antibody–drug conjugate directed to ALPP/ALPPL2 in advanced solid tumors (SGNALPV-001, trial in progress). Journal Of Clinical Oncology 2022, 40: tps3159-tps3159. DOI: 10.1200/jco.2022.40.16_suppl.tps3159.Peer-Reviewed Original ResearchMonomethyl auristatin EAdvanced solid tumorsSolid tumorsNon-small cell lungTesticular germ cell tumorsECOG PS 0Objective response rateProgression-free survivalDose-limiting toxicityPhase 1 studyDuration of responseGerm cell tumorsDisease-specific cohortsPromising preclinical dataImmunogenic cell deathClinical trial informationNormal tissue expressionAntibody-drug conjugatesMechanism of actionProtease-cleavable linkerAdult ptsCumulative safetyRECIST v1.1Exploratory endpointsMeasurable diseasePraluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial
Boni V, Fidler MJ, Arkenau HT, Spira A, Meric-Bernstam F, Uboha N, Sanborn RE, Sweis RF, LoRusso P, Nagasaka M, Garcia-Corbacho J, Jalal S, Harding JJ, Kim SK, Miedema IHC, Vugts DJ, Huisman MC, Zwezerijnen GJC, van Dongen GAMS, van Oordt C, Wang S, Dang T, Zein IA, Vasiljeva O, Lyman SK, Paton V, Hannah A, Liu JF. Praluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial. Clinical Cancer Research 2022, 28: 2020-2029. PMID: 35165101, PMCID: PMC9365353, DOI: 10.1158/1078-0432.ccr-21-3656.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsOpen-label phase I/II trialSolid tumorsPhase I/II trialPhase I/II clinical trialsBasis of tolerabilityPhase II doseBreast cancer subsetsAntibody-drug conjugatesProtease-cleavable linkerEligible patientsPosttreatment biopsiesPrior therapyStable diseaseII trialPartial responseSafety profileTumor regressionClinical trialsPrevalent subtypeCancer subsetsClinical activityMetastatic cancerBreast cancerMedian number
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 conjugates
2016
Antibody–Drug Conjugates (ADCs) in Clinical Development
McLaughlin J, LoRusso P. Antibody–Drug Conjugates (ADCs) in Clinical Development. 2016, 321-344. DOI: 10.1002/9781119060727.ch13.Peer-Reviewed Original ResearchAntibody-drug conjugatesCytotoxic agentsMonoclonal antibodiesLocal immune responseFavorable safety profileConventional cytotoxic chemotherapyConventional cytotoxic agentsDifferent antibody–drug conjugatesImmune-stimulating agentsAnti-neoplastic agentsCytotoxic chemotherapySafety profileCancer patientsIL-2Clinical trialsImmune responseClinical developmentOncologist's abilityImproved efficacyPhase IDrug conjugatesAntibodiesEfficacyTarget effectsToxicity
2013
A phase I, first-in-human study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of IMGN853 in patients (Pts) with epithelial ovarian cancer (EOC) and other FOLR1-positive solid tumors.
Kurkjian C, LoRusso P, Sankhala K, Birrer M, Kirby M, Ladd S, Hawes S, Running K, O'Leary J, Moore K. A phase I, first-in-human study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of IMGN853 in patients (Pts) with epithelial ovarian cancer (EOC) and other FOLR1-positive solid tumors. Journal Of Clinical Oncology 2013, 31: 2573-2573. DOI: 10.1200/jco.2013.31.15_suppl.2573.Peer-Reviewed Original ResearchNon-small cell lung cancerEpithelial ovarian cancerStudy drug-related serious adverse eventsAdverse eventsEndometrial cancerDose escalationDose levelsSolid tumorsAntibody-drug conjugatesRefractory non-small cell lung cancerDrug-related serious adverse eventsRefractory epithelial ovarian cancerResistant epithelial ovarian cancerClear cell renal cell cancerSerous epithelial ovarian cancerFLT-PET imagingPhase 2 doseSerious adverse eventsRefractory solid tumorsAccelerated titration designCell lung cancerRenal cell cancerPrimary study objectiveEvaluation of safetyGCIG criteria
2009
Population Pharmacokinetics of Trastuzumab-DM1, a First-in-Class HER2 Antibody-Drug Conjugate Given Every 3 Weeks (q3w) and Weekly (qw) to Patients with HER2-Positive Metastatic Breast Cancer (MBC).
LoRusso P, Girish S, Burris H, Beeram M, Vukelja S, Modi S, Yi J, Wang B, Saad O, Gupta M. Population Pharmacokinetics of Trastuzumab-DM1, a First-in-Class HER2 Antibody-Drug Conjugate Given Every 3 Weeks (q3w) and Weekly (qw) to Patients with HER2-Positive Metastatic Breast Cancer (MBC). Cancer Research 2009, 69: 5099-5099. DOI: 10.1158/0008-5472.sabcs-09-5099.Peer-Reviewed Original ResearchMetastatic breast cancerHER2-positive metastatic breast cancerHER2 antibody-drug conjugatesPhase II trialT-DM1Antibody-drug conjugatesII trialClinical factorsInter-individual variabilityTumor burdenIndividual patientsCovariate analysisPK parametersPK dataPK modelOngoing phase II trialSubsequent phase II trialTwo-compartment linear modelPhase I trialPopulation PK modelPopulation pharmacokinetic modelMultiple dose levelsConcentration-time dataAvailable PK dataPK parameter values