2021
516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial
Aix S, Calvo E, Moreno V, Garralda E, Cervantes A, Ramalingam S, Pérez J, LoRusso P, Furqan M, Cho D, Muik A, Lagkadinou E, Türeci Ö, Couto S, Pencheva N, Forssmann U, Şahin U, Ahmadi T, Higgs B, Jure-Kunkel M, Melero I. 516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial. Journal For ImmunoTherapy Of Cancer 2021, 9: a546-a546. DOI: 10.1136/jitc-2021-sitc2021.516.Peer-Reviewed Original ResearchPrior anti-PD-1 therapyAnti-PD-1 therapyPD-L1NK cellsTumor reductionAnti-PD-1 combination therapyEffector memory T cellsPD-L1 blockadePhase 1/2a trialPrior systemic therapySoluble immune mediatorsTumor PD-L1Disease control rateAdvanced solid tumorsAntitumor immune responseSubset of patientsMemory T cellsSerial blood samplesImproved clinical efficacyTumor biopsy specimensCycle 1Tumor biopsy samplesEthics committees/institutional review boardsInstitutional review boardCycle 2A 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
2016
A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function
Li C, Agarwal P, Gibiansky E, Jin J, Dent S, Gonçalves A, Nijem I, Strasak A, Harle-Yge M, Chernyukhin N, LoRusso P, Girish S. A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function. Clinical Pharmacokinetics 2016, 56: 1069-1080. PMID: 27995530, DOI: 10.1007/s40262-016-0496-y.Peer-Reviewed Original ResearchConceptsNormal hepatic functionModerate hepatic impairmentHepatic impairmentMetastatic breast cancerHepatic functionTrastuzumab emtansineBreast cancerCycle 1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Phase I pharmacokinetic studyHuman epidermal growth factor receptorChild-Pugh criteriaMild hepatic impairmentT-DM1 3.6T-DM1 exposureGrowth factor receptor 2I pharmacokinetic studyFactor receptor 2Epidermal growth factor receptorGrowth factor receptorModerate cohortBaseline albuminT-DM1
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
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
2009
Tremelimumab in combination with exemestane as novel immunotherapy for patients with advanced breast cancer
Vonderheide R, LoRusso P, Khalil M, Heath E, Khaira D, Soulieres D, Dorazio P, Mariani G, Usari T, Domchek S. Tremelimumab in combination with exemestane as novel immunotherapy for patients with advanced breast cancer. Journal Of Clinical Oncology 2009, 27: 3034-3034. DOI: 10.1200/jco.2009.27.15_suppl.3034.Peer-Reviewed Original ResearchBreast cancerHormone receptor breast cancerAnti-CTLA4 monoclonal antibodySingle-agent doseUnknown receptor statusCycles of therapyPhase II doseSingle-agent antitumor activityAdvanced breast cancerDose-escalation trialSerum transaminase elevationTumor response evaluationCycle 1Assessment of safetyStable diseaseAdvanced diseasePrimary endpointSecondary endpointsTransaminase elevationAutoimmune thyroiditisHormone replacementNovel immunotherapiesObjective responsePharmacokinetic interactionsReceptor status