2023
A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas
Gounder M, Bauer T, Schwartz G, Weise A, LoRusso P, Kumar P, Tao B, Hong Y, Patel P, Lu Y, Lesegretain A, Tirunagaru V, Xu F, Doebele R, Hong D. A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas. Journal Of Clinical Oncology 2023, 41: 1714-1724. PMID: 36669146, PMCID: PMC10022862, DOI: 10.1200/jco.22.01285.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalDisease control rateProgression-free survivalControl rateDedifferentiated liposarcomaGrade 3/4 drug-related adverse eventsMurine double minute 2 inhibitorsSolid tumorsIntermittent scheduleDrug-related adverse eventsHuman Phase I StudyRandomized phase III trialPhase II doseAdvanced solid tumorsPhase III trialsIntermittent dosing scheduleSingle-agent activityPhase I studiesHuman phase IAdvanced liposarcomaAdverse eventsIII trialsDosing schedulesAdvanced cancerEfficacy analysis
2022
A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance.
Yap T, LoRusso P, Wong D, Hu-Lieskovan S, Papadopoulos K, Holz J, Grabowska U, Gradinaru C, Leung K, Marshall S, Reader C, Russell R, Sainson R, Seal C, Shepherd C, Germaschewski F, Gliddon D, Stern O, Young L, Brewis N, Kayitalire L, Morrow M. A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance. Clinical Cancer Research 2022, 29: 888-898. PMID: 36342102, DOI: 10.1158/1078-0432.ccr-22-1449.Peer-Reviewed Original ResearchConceptsDisease control rateLAG-3PD-L1Advanced cancerOverall disease control rateDisease controlPeripheral effector cellsPhase 2 doseSerious adverse eventsPhase 1 studySoluble LAG-3Tetravalent bispecific antibodyPrior regimensStable diseaseDose expansionMetastatic settingAdverse eventsPartial responseEffector cellsClinical benefitControl rateSustained elevationTitration designPharmacodynamic activityHuman studies
2020
PROCLAIM-CX-072: Analysis of patients with advanced solid tumors receiving long-term treatment with CX-072, a PD-L1 probody therapeutic, as a single agent or in combination with ipilimumab.
Thistlethwaite F, Naing A, Gil-Martin M, LoRusso P, Randhawa M, Eskens F, Sanborn R, Uboha N, Cho D, Spira A, Bondarenko I, Plummer E, Garcia-Corbacho J, Victoria I, Lavernia J, Melero I, De Vries E, Garner W, Arkenau H, Bendell J. PROCLAIM-CX-072: Analysis of patients with advanced solid tumors receiving long-term treatment with CX-072, a PD-L1 probody therapeutic, as a single agent or in combination with ipilimumab. Journal Of Clinical Oncology 2020, 38: 3005-3005. DOI: 10.1200/jco.2020.38.15_suppl.3005.Peer-Reviewed Original ResearchImmune-related AEImmune checkpoint inhibitorsCX-072Tumor microenvironmentDisease control rateLong-term therapyMo of treatmentDose-response effectMultiple tumor typesMonotherapy doseCheckpoint inhibitorsDose modificationDose escalationPD-L1Control rateTreatment durationTumor typesIPI 3Enhanced efficacyMonotherapyEfficacyQ2WQ3W.PatientsProbody
2017
Phase I study combining the aurora kinase A (AURKA) inhibitor alisertib (Ali) with mFOLFOX in gastrointestinal (GI) cancer.
Goff L, Azad N, Stein S, Whisenant J, Vaishampayan U, Hochster H, Connolly R, Weise A, LoRusso P, El-Rifai W, Berlin J. Phase I study combining the aurora kinase A (AURKA) inhibitor alisertib (Ali) with mFOLFOX in gastrointestinal (GI) cancer. Journal Of Clinical Oncology 2017, 35: 2593-2593. DOI: 10.1200/jco.2017.35.15_suppl.2593.Peer-Reviewed Original ResearchGI cancersStandard platinum-based therapyCorrelative biomarker studyDisease control rateMost frequent toxicitiesPreliminary clinical activityPlatinum-based therapyMajority of ptsEvaluable ptsStable diseaseEligible patientsFrequent toxicitiesHematologic toxicityPartial responseStandard therapyDose escalationInhibition of AURKAControl rateGastrointestinal cancerPreclinical dataClinical activityPlatinum agentsDose levelsInhibitor alisertibOptimal timing window
2013
A phase I dose-escalation and PK study of continuous oral rucaparib in patients with advanced solid tumors.
Kristeleit R, Shapiro G, LoRusso P, Infante J, Flynn M, Patel M, Tolaney S, Hilton J, Calvert A, Giordano H, Isaacson J, Borrow J, Allen A, Jaw-Tsai S, Burris H. A phase I dose-escalation and PK study of continuous oral rucaparib in patients with advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2585-2585. DOI: 10.1200/jco.2013.31.15_suppl.2585.Peer-Reviewed Original ResearchAdvanced solid tumorsOral rucaparibStable diseaseTrough levelsSolid tumorsIntra-patient dose escalationOverall disease control rateTreatment-related adverse eventsOral small-molecule inhibitorDose-proportional PKDurable stable diseaseLow interpatient variabilityPhase 2 doseDisease control rateDose-escalation designDose cohortsBID dosingAdverse eventsObjective responsePK assessmentDose escalationEscalation designControl rateQD dosingStandard treatment
2012
Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulin-like growth factor receptor (IGF-1R), administered in combination with anticancer therapies to patients with advanced solid tumors
Macaulay V, Middleton M, Protheroe A, Tolcher A, Dieras V, Sessa C, Bahleda R, Blay J, LoRusso P, Mery-Mignard D, Soria J. Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulin-like growth factor receptor (IGF-1R), administered in combination with anticancer therapies to patients with advanced solid tumors. Annals Of Oncology 2012, 24: 784-791. PMID: 23104723, PMCID: PMC3574548, DOI: 10.1093/annonc/mds511.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsDeoxycytidineDiarrheaDocetaxelDoxorubicinErlotinib HydrochlorideFemaleGemcitabineHumansLeiomyosarcomaMaleMelanomaMiddle AgedQuinazolinesReceptor, IGF Type 1Skin NeoplasmsSoft Tissue NeoplasmsTaxoidsTreatment OutcomeConceptsAdvanced solid tumorsInsulin-like growth factor receptorType 1 insulin-like growth factor receptorGrowth factor receptorIGF-IISolid tumorsDisease controlCommon adverse eventsFactor receptorIGF-1R antibodyDurable disease controlCohort C2Adverse eventsPartial responseCohort BDocetaxel administrationSteroid premedicationControl ratePK interactionsGrade 3IGF-BP3Blood samplesCohort C1PatientsAVE1642
2009
Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC)
Gadgeel S, Wozniak A, Edelman M, Valdivieso M, Heilbrun L, Venkatramanamoorthy R, Shields A, LoRusso P, Hackstock D, Ruckdeschel J. Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2009, 27: e19007-e19007. DOI: 10.1200/jco.2009.27.15_suppl.e19007.Peer-Reviewed Original ResearchNon-small cell lung cancerRecurrent non-small cell lung cancerFLT-PET scansNSCLC ptsDose reductionPET scansMeasurable non-small cell lung cancerConfirmed response rateDisease control ratePhase II trialMedian age 60Cell lung cancerStandard uptake valueVEGF receptor 1Males 56Pemetrexed combinationsPrior regimensBrain metastasesGrade 3/4II trialVEGF therapyMajor hemorrhageOral inhibitorControl rateLung cancer