2024
The 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 2 study of the WEE1 inhibitor AZD1775 in SETD2-deficient advanced solid tumor malignancies.
Maldonado E, Rathmell W, Shapiro G, Rodon Ahnert J, Mahalingam D, Trikalinos N, Rezazadeh A, Adorno Febles V, Parikh M, Boerner S, Krings G, Takebe N, LoRusso P, Aggarwal R. A phase 2 study of the WEE1 inhibitor AZD1775 in SETD2-deficient advanced solid tumor malignancies. Journal Of Clinical Oncology 2023, 41: 3104-3104. DOI: 10.1200/jco.2023.41.16_suppl.3104.Peer-Reviewed Original ResearchClear cell renal cell carcinomaSolid tumor malignanciesClinical benefit rateObjective response rateDuration of responseTumor malignancyEvaluable ptsStable diseaseObjective responseAdverse eventsTumor regressionMetastatic clear cell renal cell carcinomaAdvanced solid tumor malignanciesMetastatic solid tumor malignanciesCommon adverse eventsDurable stable diseaseECOG PS 0RECIST 1.1 criteriaSubset of ptsPhase 2 studyCohort of patientsCell renal cell carcinomaNext-generation sequencing panelBest overall responseRenal cell carcinomaTrial in progress: A phase 1, first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of ASP3082 in patients with previously treated advanced solid tumors and KRAS G12D mutations.
Tolcher A, Park W, Wang J, Spira A, Janne P, Lee H, Gill S, LoRusso P, Herzberg B, Goldman J, Morgensztern D, Berlin J, Kasi A, Fujii H, Pelster M. Trial in progress: A phase 1, first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of ASP3082 in patients with previously treated advanced solid tumors and KRAS G12D mutations. Journal Of Clinical Oncology 2023, 41: tps764-tps764. DOI: 10.1200/jco.2023.41.4_suppl.tps764.Peer-Reviewed Original ResearchKRAS G12DAdverse eventsLung cancerKRAS G12D mutationCancer cellsEastern Cooperative Oncology Group performance statusSolid tumorsNon-small cell lung cancerMetastatic solid tumor malignanciesSolid Tumors version 1.1Dose-escalation cohortsDose-expansion studyPhase 2 doseDisease control rateObjective response rateSerious adverse eventsAdvanced solid tumorsResponse Evaluation CriteriaDose-limiting toxicityPancreatic ductal cancerPhase 1 studyCell lung cancerDuration of responseSolid tumor malignanciesG12D mutation
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 diseaseMulticenter 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 efficacy of the anti-CD73 monoclonal antibody (mAb) oleclumab ± durvalumab in patients (pts) with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or EGFR-mutant non-small cell lung cancer (EGFRm NSCLC).
Bendell J, LoRusso P, Overman M, Noonan A, Kim D, Strickler J, Kim S, Clarke S, George T, Grimison P, Barve M, Amin M, Desai J, Wise-Draper T, Cooper Z, Elgeioushi N, Mueller N, Kumar R, Wu K, Patel S. Safety and efficacy of the anti-CD73 monoclonal antibody (mAb) oleclumab ± durvalumab in patients (pts) with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or EGFR-mutant non-small cell lung cancer (EGFRm NSCLC). Journal Of Clinical Oncology 2021, 39: 9047-9047. DOI: 10.1200/jco.2021.39.15_suppl.9047.Peer-Reviewed Original ResearchTreatment-related adverse eventsPancreatic ductal adenocarcinomaCommon treatment-related adverse eventsAdvanced colorectal cancerObjective responseCombination therapyColorectal cancerEGFRm NSCLCEscalation phaseNSCLC ptsEGFR-mutant non-small cell lung cancerNon-small cell lung cancerMicrosatellite stable colorectal cancerTolerable safety profileUpregulation of CD73Cell lung cancerDuration of responseStable colorectal cancerRECIST v1.1Expansion cohortPrevious interim analysisClinical responseData cutoffLocal immunosuppressionManageable safety
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
2012
Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.
Modi S, Elias A, LoRusso P, Samant M, Guardino E, Althaus B, Krop I. Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab. Journal Of Clinical Oncology 2012, 30: 528-528. DOI: 10.1200/jco.2012.30.15_suppl.528.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerMetastatic breast cancerT-DM1Prior systemic therapyPhase Ib studyPhase II studyDose-escalation studySingle-agent activityDuration of responseDose escalation schemeFuture clinical trialsDLT criteriaII studyMedian ageSystemic therapyExtension trialPreclinical dataTrastuzumab emtansineClinical trialsMedian numberToxicity CriteriaBreast cancerIb studyPhase IbQ3w
2006
Phase I evaluation of AZD2171, a highly potent and selective inhibitor of VEGFR signaling, in combination with selected chemotherapy regimens in patients with advanced solid tumors
Lorusso P, Heath E, Valdivieso M, Pilat M, Wozniak A, Gadgeel S, Shields A, Puchalski T, Ewesuedo R. Phase I evaluation of AZD2171, a highly potent and selective inhibitor of VEGFR signaling, in combination with selected chemotherapy regimens in patients with advanced solid tumors. Journal Of Clinical Oncology 2006, 24: 3034-3034. DOI: 10.1200/jco.2006.24.18_suppl.3034.Peer-Reviewed Original ResearchVascular endothelial growth factor receptorDose-limiting toxicityArm 1Chemotherapy regimensArm 2Arm 4Grade 3 hand-foot syndromeSolid tumorsGrade 4 neutropenic feverGrade 3 diarrheaGrade 3 fatigueGrade 3 hypertensionHand-foot syndromePhase I evaluationPre-treated patientsAdvanced solid tumorsPhase I trialEndothelial growth factor receptorSolid tumor patientsDuration of responseSelective inhibitorEfficacy/toxicityGrowth factor receptorIdentical chemotherapyNeutropenic fever