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
2019
Phase 1, first-in-human study of TRAIL receptor agonist fusion protein ABBV-621.
Ratain M, Doi T, De Jonge M, LoRusso P, Dunbar M, Chiney M, Motwani M, Glasgow J, Petrich A, Rasco D, Calvo E. Phase 1, first-in-human study of TRAIL receptor agonist fusion protein ABBV-621. Journal Of Clinical Oncology 2019, 37: 3013-3013. DOI: 10.1200/jco.2019.37.15_suppl.3013.Peer-Reviewed Original ResearchDose escalationDose-limiting toxicityBlood-based markersECOG 0Prior regimensStable diseaseAcceptable toxicityMedian durationRespiratory failureMedian agePartial responseColorectal cancerPancreatic cancerBlood bilirubinBayesian continual reassessment methodPD markersContinual reassessment methodHuman studiesDay 1Solid tumorsTumor typesPK studiesTumor modelAntitumor activityApoptotic cell deathCX-072, a PD-L1 Probody therapeutic, as monotherapy in patients with advanced solid tumors: Preliminary results of PROCLAIM-CX-072.
Naing A, Thistlethwaite F, Spira A, Garcia-Corbacho J, Randhawa M, Eskens F, O'Neil B, Lavernia J, Uboha N, Hamid O, El-Khoueiry A, Benson B, Garner W, Huels V, Arkenau H, LoRusso P. CX-072, a PD-L1 Probody therapeutic, as monotherapy in patients with advanced solid tumors: Preliminary results of PROCLAIM-CX-072. Journal Of Clinical Oncology 2019, 37: 2513-2513. DOI: 10.1200/jco.2019.37.15_suppl.2513.Peer-Reviewed Original ResearchCutaneous squamous cell carcinomaSquamous cell carcinomaSmall bowel adenocarcinomaCX-072Advanced solid tumorsAdverse eventsSolid tumorsPD-L1Cell carcinomaSkin lesionsAnti-programmed cell death ligand-1 (PD-L1) immunotherapiesGrade 3/4 treatment-related adverse eventsAnal squamous cell carcinomaDeath ligand 1 (PD-L1) immunotherapyStandard curative treatment optionsTreatment-related adverse eventsTriple-negative breast cancerAnti-CTLA4 treatmentPhase 1/2a studyMedian treatment durationCurative treatment optionPD-L1 expressionUnresectable solid tumorsPrior regimensBowel adenocarcinoma
2017
A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors
Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmaña J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clinical Cancer Research 2017, 23: 4095-4106. PMID: 28264872, DOI: 10.1158/1078-0432.ccr-16-2796.Peer-Reviewed Original ResearchConceptsHigh-grade ovarian carcinomaObjective response rateInvestigator-assessed objective response rateOral rucaparibAdverse eventsCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsAspartate transaminase elevationsAsthenia/fatigueProtocol-defined criteriaRECIST version 1.1Phase II doseAdvanced solid tumorsProgression-free intervalSmall molecule PARP inhibitorsClin Cancer ResManageable toxicityPrior regimensPrimary endpointTransaminase elevationPlatinum therapyMultiple dosesOvarian carcinomaAlanine transaminaseClinical activity
2013
Phase II clinical activity and tolerability of the SMAC-mimetic birinapant (TL32711) plus irinotecan in irinotecan-relapsed/refractory metastatic colorectal cancer.
Senzer N, LoRusso P, Martin L, Schilder R, Amaravadi R, Papadopoulos K, Segota Z, Weng D, Graham M, Adjei A. Phase II clinical activity and tolerability of the SMAC-mimetic birinapant (TL32711) plus irinotecan in irinotecan-relapsed/refractory metastatic colorectal cancer. Journal Of Clinical Oncology 2013, 31: 3621-3621. DOI: 10.1200/jco.2013.31.15_suppl.3621.Peer-Reviewed Original ResearchMedian progression-free survivalProgression-free survivalClinical activityRefractory/BP riskOverall clinical benefit rateRefractory metastatic colorectal cancerKRAS-MTBest supportive careClinical benefit rateMetastatic colorectal cancerReversible side effectsPhase 1 studySMAC mimetic birinapantAnti-tumor synergyPrior regimensSupportive careClinical benefitColorectal cancerKRAS WTOngoing treatmentSmac mimeticsBenefit rateMedian numberTherapeutic synergy
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