2024
First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors
Shimizu T, Powderly J, Razak A, LoRusso P, Miller K, Kao S, Kongpachith S, Tribouley C, Graham M, Stoll B, Patel M, Sahtout M, Blaney M, Leibman R, Golan T, Tolcher A. First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors. Frontiers In Oncology 2024, 14: 1376551. DOI: 10.3389/fonc.2024.1376551.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-escalation phaseDose escalationSolid tumorsSurface of regulatory T cellsRecommended phase 2 doseSuppress antitumor immune responsesCombination therapy cohortsDose-proportional PKMonotherapy-treated patientsPhase 2 doseMedian response durationAntitumor immune responseDose-limiting toxicityTherapy-treated patientsRegulatory T cellsMaximum administered doseFirst-in-humanDose escalation resultsGlycoprotein A repetitionsPromote tumor growthBlood biomarker dataDose expansionPretreated patientsEscalating dosesPhase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors.
Falchook G, LoRusso P, Goldman J, El-Khoueiry A, Tolcher A, Xing Y, Henry J, Keam B, Kim D, Kim T, Kim H, Hong M, Kim M, Lee D, Lee S, Jeon J, Hayslip J, Xu C, Garon E. Phase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors. Journal Of Clinical Oncology 2024, 42: 2529-2529. DOI: 10.1200/jco.2024.42.16_suppl.2529.Peer-Reviewed Original ResearchTreatment related adverse eventsClinical benefit rateOverall response ratePD-L1Dose levelsPD-(L)1Complete responsePartial responseSolid tumorsHead and neck squamous cellAntibody targeting PD-L1Treated with checkpoint inhibitorsActivation of T cellsDose-limiting toxicityPre-treated patientsPD-(L)1 inhibitorsDose-expansion cohortRelapsed/refractory solid tumorsWeight-based dosingLines of treatmentPD-L1 antagonistsRelated adverse eventsAnti-tumor effectsDose-dependent increaseMultiple tumor typesA phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation.
Stockton S, Shyr C, Cecchini M, Aljumaily R, Halfdanarson T, Sonbol M, Whisenant J, Ivy S, LoRusso P, Das S, Gore S, Berlin J, Beumer J, Heumann T. A phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation. Journal Of Clinical Oncology 2024, 42: 3076-3076. DOI: 10.1200/jco.2024.42.16_suppl.3076.Peer-Reviewed Original ResearchMaximum tolerated doseDose escalationDose levelsMedian progression-free survivalRecommended phase 2 doseRefractory advanced solid tumorsResults of dose escalationTreatment-related adverse eventsSmall cell lung cancerDisease control ratePhase 2 dosePhase Ia studyDose-limiting toxicityProgression-free survivalAdvanced solid tumorsPhase I studyCell lung cancerAnti-tumor activityExpansion cohortPartial responseTolerated doseTopotecan exposureStudy drugCancer xenograftsRespiratory failureEntinostat, 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, 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 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 first-in-class phase 1/2a study of the next generation CDK4-selective inhibitor PF-07220060 in patients (pts) with advanced solid tumors, enriched for HR+ HER2- mBC who progressed on prior CDK4/6 inhibitors and endocrine therapy.
Yap T, Giordano A, Hamilton E, LoRusso P, Bowers M, Basu C, Billotte S, Delioukina M, Liu F, Yang J, Sharma M. First-in-human first-in-class phase 1/2a study of the next generation CDK4-selective inhibitor PF-07220060 in patients (pts) with advanced solid tumors, enriched for HR+ HER2- mBC who progressed on prior CDK4/6 inhibitors and endocrine therapy. Journal Of Clinical Oncology 2023, 41: 3009-3009. DOI: 10.1200/jco.2023.41.16_suppl.3009.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsHR+/HER2- MBCEndocrine therapySolid tumorsCDK4/6 inhibitorsMedian progression-free survivalClinical benefit responseMedian prior linesDose-limiting toxicityProgression-free survivalAdvanced/metastatic breast cancerPhase 1/2a studyLines of treatmentFirst-in-humanDose-dependent increaseAnti-tumor activityDose expansionHER2-MBCSecondary/exploratory objectivesDose escalationData cutoffECOG PSSystemic therapyMedian ageMulticenter trialTrial 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
A 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 activityNCI 9938: Phase I clinical trial of ATR inhibitor berzosertib (M6620, VX-970) in combination with irinotecan in patients with advanced solid tumors.
Villaruz L, Kelly K, Waqar S, Davis E, Shapiro G, LoRusso P, Dees E, Normolle D, Rhee J, Chu E, Gore S, Beumer J. NCI 9938: Phase I clinical trial of ATR inhibitor berzosertib (M6620, VX-970) in combination with irinotecan in patients with advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 3012-3012. DOI: 10.1200/jco.2022.40.16_suppl.3012.Peer-Reviewed Original ResearchDose-limiting toxicityExperienced dose-limiting toxicityCell lung cancerColorectal cancerPancreatic cancerLung cancerDose levelsSolid tumorsNon-small cell lung cancerCommon treatment-related gradeGrade 3 lung infectionStage IISmall cell lung cancerPhase I clinical trialDose-expansion cohortsGrade 3 diarrheaMutant solid tumorsPhase II doseTreatment-related gradeGrade 2 diarrheaAdvanced solid tumorsManageable side effectsDose-escalation designMutant colorectal cancerEfficacy of irinotecanPhase 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 disease
2021
484 Preliminary efficacy of the IL-15 superagonist SO-C101 in combination with pembrolizumab in patients with advanced/metastatic solid tumors
Garralda E, Galvao V, Champiat S, LoRusso P, Grell P, Naing A, Janku F, Sachse R, Bechard D, Kiemle-Kallee J, Marabelle A, Garralda E. 484 Preliminary efficacy of the IL-15 superagonist SO-C101 in combination with pembrolizumab in patients with advanced/metastatic solid tumors. Journal For ImmunoTherapy Of Cancer 2021, 9: a514-a514. DOI: 10.1136/jitc-2021-sitc2021.484.Peer-Reviewed Original ResearchStudy drug-related adverse eventsDrug-related adverse eventsCytokine release syndromeDose-limiting toxicityAdverse eventsCommon study drug-related adverse eventsAnti-programmed cell death protein 1 antibodyGrade 3 cytokine release syndromeSolid tumorsCell death protein 1 antibodyAnti-PD-1 therapyLong-term stable diseaseLocal injection site reactionsSkin squamous cell carcinomaPhase 2 dosePrevious systemic therapyTreatment-related deathsInjection site reactionsMetastatic solid tumorsAdditional clinical benefitDose-escalation designProtective memory responsesProtein 1 antibodySquamous cell carcinomaAvailable safety data502 Recommended phase 2 dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the IL-15 superagonist SO-C101 as monotherapy in patients with advanced/metastatic solid tumors
Marabelle A, Champiat S, Galvao V, Naing A, Janku F, LoRusso P, Grell P, Sachse R, Bechard D, Kiemle-Kallee J, Garralda E. 502 Recommended phase 2 dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the IL-15 superagonist SO-C101 as monotherapy in patients with advanced/metastatic solid tumors. 2021, a534-a534. DOI: 10.1136/jitc-2021-sitc2021.502.Peer-Reviewed Original ResearchPhase 2 doseDose-limiting toxicityAdverse eventsPartial responseStable diseaseTransaminase increaseSolid tumorsDrug-related adverse eventsIL-15 receptor αCutaneous squamous cell carcinomaLocal injection site reactionsPrevious systemic therapyResults Thirty patientsSignificant partial responseTreatment-related deathsCommon adverse eventsFlu-like syndromeRelated adverse eventsInjection site reactionsMetastatic solid tumorsAdditional clinical benefitDose-escalation designSquamous cell carcinomaDose-dependent increaseT cell activation493 First-in-human phase 1/2 trial to evaluate the safety and initial clinical activity of DuoBody®-CD40×4–1BB (GEN1042) in patients with advanced solid tumors
Johnson M, Lopez J, LoRusso P, Bauman J, Haggstrom D, Lagkadinou E, Bajaj G, Türeci Ö, Adams H, Şahin U, Fu Y, Ahmadi T, Rohrberg K. 493 First-in-human phase 1/2 trial to evaluate the safety and initial clinical activity of DuoBody®-CD40×4–1BB (GEN1042) in patients with advanced solid tumors. Journal For ImmunoTherapy Of Cancer 2021, 9: a525-a525. DOI: 10.1136/jitc-2021-sitc2021.493.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-limiting toxicityAdverse eventsSolid tumorsPartial responseLung cancerAntitumor activityNon-CNS solid tumorsTreatment-related adverse eventsEffector memory T cellsDrug-related gradeInitial clinical activityPD-1 inhibitorsPhase 1/2 trialTumor-specific immunityMemory T cellsCell lung cancerFavorable safety profilePreliminary antitumor activityNeuroendocrine lung cancerBest overall responseEnd of infusionCommon cancer typesEthics committees/institutional review boardsInstitutional review boardA 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 models
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 windowPhase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti–c-Met Antibody, in Patients with Advanced Solid Tumors
Strickler JH, LoRusso P, Salgia R, Kang YK, Yen C, Lin CC, Ansell P, Motwani M, Wong S, Yue H, Wang L, Reilly E, Afar D, Naumovski L, Ramanathan RK. Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti–c-Met Antibody, in Patients with Advanced Solid Tumors. Molecular Cancer Therapeutics 2020, 19: 1210-1217. PMID: 32127466, DOI: 10.1158/1535-7163.mct-19-0529.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsSolid tumorsStable diseaseDose escalationCommon treatment-related adverse eventsAnti-c-Met antibodyTreatment-related adverse eventsDose-expansion phaseI Dose-EscalationAcceptable safety profileResponse Evaluation CriteriaDose-limiting toxicitySubset of patientsLinear pharmacokinetic profilePeak plasma concentrationAcute infusion reactionsHuman phase IDose cohortsDose expansionRECIST criteriaAdverse eventsEscalation cohortsInfusion reactionsObjective responsePartial response
2019
457P First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumours: Dose-optimization cohorts
Calvo E, de Jonge M, Rasco D, Moreno V, Chang Y, Chiney M, Motwani M, Penugonda S, Petrich A, Ratain M, LoRusso P. 457P First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumours: Dose-optimization cohorts. Annals Of Oncology 2019, 30: v169-v170. DOI: 10.1093/annonc/mdz244.019.Peer-Reviewed Original ResearchDose levelsPancreatic cancerNon-cardiac chest painGenentech/RochePhase 2 dosePrior treatment regimensAntitumor activityAcceptable safety profileDose-limiting toxicityRoche/GenentechDeath receptor 4Bristol-Myers SquibbEligible ptsPleuritic painStable diseaseChest painGrade 3/4Respiratory failureMedian durationPartial responseToxic hepatitisDose escalationTreatment regimensSafety profileConclusion Administration1198P FPA150 (B7-H4 antibody) phase I update in advanced solid tumours: Monotherapy and in combination with pembrolizumab
Wainberg Z, Sachdev J, Bauer T, Pant S, Chawla S, Marina N, Xiang H, Deng W, Schmidt M, Patnaik A, LoRusso P. 1198P FPA150 (B7-H4 antibody) phase I update in advanced solid tumours: Monotherapy and in combination with pembrolizumab. Annals Of Oncology 2019, 30: v489. DOI: 10.1093/annonc/mdz253.024.Peer-Reviewed Original ResearchTreatment-related adverse eventsAdvanced solid tumorsB7-H4Prime TherapeuticsSolid tumorsAdverse eventsEli LillyTreatment-related serious adverse eventsAntibody-dependent cell-mediated cytotoxicityAnti-PD1 agentsB7-H4 antibodyDose-proportional exposureSerious adverse eventsDose-limiting toxicityCell-mediated cytotoxicityCommon being diarrheaGlaxo Smith KlineBristol-Myers SquibbDrug discontinuationGuardant HealthKaryopharm TherapeuticsSarcoma AllianceDose expansionDose escalationOngoing trials