2023
1029P Dazostinag (TAK-676) alone and in combination with pembrolizumab (pembro) in patients (pts) with advanced or metastatic solid tumors: Preliminary safety, PK/PD, and anti-tumor activity in a phase I dose escalation study supporting a recommended dose for expansion (RDE)
Olszanski A, Luke J, LoRusso P, Falchook G, Bedard P, Sanborn R, Patel S, Orr D, Gibbs J, Li C, Huang Y, Gregory R, Perera S, Xu R, Joshi A, Lee M, Raizer J, Gao X. 1029P Dazostinag (TAK-676) alone and in combination with pembrolizumab (pembro) in patients (pts) with advanced or metastatic solid tumors: Preliminary safety, PK/PD, and anti-tumor activity in a phase I dose escalation study supporting a recommended dose for expansion (RDE). Annals Of Oncology 2023, 34: s625-s626. DOI: 10.1016/j.annonc.2023.09.2168.Peer-Reviewed Original Research
2022
172P Phase I study of JTX-8064, a LILRB2 (ILT4) inhibitor, as monotherapy and combination with pimivalimab (pimi), a PD-1 inhibitor (PD-1i), in patients (pts) with advanced solid tumors
Papadopoulos K, Li T, Lakhani N, Powderly J, George T, Teoh D, Kilari D, Giaccone G, Sanborn R, Ghamande S, LoRusso P, Gibney G, Ma V, Yalamanchili K, Brown J, Mota N, Kadra C, Umiker B, Xiao X, Trehu E. 172P Phase I study of JTX-8064, a LILRB2 (ILT4) inhibitor, as monotherapy and combination with pimivalimab (pimi), a PD-1 inhibitor (PD-1i), in patients (pts) with advanced solid tumors. Immuno-Oncology Technology 2022, 16: 100284. DOI: 10.1016/j.iotech.2022.100284.Peer-Reviewed Original Research770 Safety, efficacy, and pharmacokinetic results from a phase I first-in-human study of ABBV-151 with or without anti-PD1 mAb (budigalimab) in patients with locally advanced or metastatic solid tumors
Tolcher A, Roda-Perez D, He K, Moreno V, Gomez-Roca C, Machiels J, Razak A, Sahtout M, Guan X, Jaryno-Daly S, Leibman R, Blaney M, O’Brien J, Lorusso P, Powderly J, Golan T, Miller K, Bruix J. 770 Safety, efficacy, and pharmacokinetic results from a phase I first-in-human study of ABBV-151 with or without anti-PD1 mAb (budigalimab) in patients with locally advanced or metastatic solid tumors. 2022, a801-a801. DOI: 10.1136/jitc-2022-sitc2022.0770.Peer-Reviewed Original ResearchOA03.04 Phase I A Study to Evaluate GDC-6036 Monotherapy in Patients with Non-small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation
Sacher A, Patel M, Miller W, Desai J, Garralda E, Bowyer S, Kim T, De Miguel M, Falcon A, Krebs M, Lee J, Cheng M, Han S, Shacham-Shmueli E, Forster M, Jerusalem G, Massarelli E, Rodriguez L, Prenen H, Walpole I, Arbour K, Choi Y, Dharia N, Lin M, Mandlekar S, Joo S, Shi Z, Schutzman J, LoRusso P. OA03.04 Phase I A Study to Evaluate GDC-6036 Monotherapy in Patients with Non-small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation. Journal Of Thoracic Oncology 2022, 17: s8-s9. DOI: 10.1016/j.jtho.2022.07.023.Peer-Reviewed Original ResearchFirst in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response
Yap TA, Gainor JF, Callahan MK, Falchook GS, Pachynski RK, LoRusso P, Kummar S, Gibney GT, Burris HA, Tykodi SS, Rahma OE, Seiwert TY, Papadopoulos KP, Murphy M, Park H, Hanson A, Hashambhoy-Ramsay Y, McGrath L, Hooper E, Xiao X, Cohen H, Fan M, Felitsky D, Hart C, McComb R, Brown K, Sepahi A, Jimenez J, Zhang W, Baeck J, Laken H, Murray R, Trehu E, Harvey CJ. First in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response. Clinical Cancer Research 2022, 28: 3695-3708. PMID: 35511938, PMCID: PMC9433959, DOI: 10.1158/1078-0432.ccr-21-4256.Peer-Reviewed Original ResearchConceptsSubset of patientsPredictive biomarkersPharmacodynamic biomarkersModest objective response rateNon-small cell lung cancer trialsCD4 T cell populationCell lung cancer trialsPhase IObjective response ratePhase II doseAdvanced solid tumorsCD4 T cellsFavorable safety profilePotential predictive biomarkersLung cancer trialsPredictors of responseT cell populationsGreater clinical benefitClinical outcomesClinical benefitSafety profileCancer trialsNivolumabT cellsPatients
2021
1033TiP A first-in-human phase I study of FS120, an OX40/CD137 tetravalent bispecific antibody, in patients with advanced malignancies
Papadopoulos K, Yap T, Piha-Paul S, Lorusso P, Hu-Lieskovan S, Shepherd C, Marshall S, Holz J, Poon E, Grabowska U, Kayitalire L. 1033TiP A first-in-human phase I study of FS120, an OX40/CD137 tetravalent bispecific antibody, in patients with advanced malignancies. Annals Of Oncology 2021, 32: s864-s865. DOI: 10.1016/j.annonc.2021.08.1417.Peer-Reviewed Original Research
2020
Phase I first-in-human study of ABBV-151 as monotherapy or in combination with budigalimab in patients with locally advanced or metastatic solid tumours
Powderly J, Shimizu T, Lorusso P, Razak A, Miller K, Balar A, Bruix J, Michel L, Blaney M, Guan X, Lacy S, Lally S, Lambert S, Leibman R, Vosganian G, Golan T, Tolcher A. Phase I first-in-human study of ABBV-151 as monotherapy or in combination with budigalimab in patients with locally advanced or metastatic solid tumours. Annals Of Oncology 2020, 31: s499. DOI: 10.1016/j.annonc.2020.08.710.Peer-Reviewed Original ResearchA First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors
Varga A, Soria JC, Hollebecque A, LoRusso P, Bendell J, Huang SA, Wagle MC, Okrah K, Liu L, Murray E, Sanabria-Bohorquez SM, Tagen M, Dokainish H, Mueller L, Burris H. A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors. Clinical Cancer Research 2020, 26: 1229-1236. PMID: 31848189, DOI: 10.1158/1078-0432.ccr-19-2574.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedDose-Response Relationship, DrugFatigueFemaleHumansMaleMAP Kinase Signaling SystemMaximum Tolerated DoseMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NauseaNeoplasmsPatient SafetyProtein Kinase InhibitorsPyridonesPyrimidinesTissue DistributionVomitingConceptsBRAF-mutant colorectal cancerColorectal cancerAdverse eventsFDG-PETCommon drug-related adverse eventsSolid tumorsDrug-related adverse eventsPhase IPartial metabolic responseAcceptable safety profileAdvanced solid tumorsDose-proportional increaseGrade 3 rashMetastatic solid tumorsSerial tumor biopsiesSingle-agent activityBest overall responseHuman phase IMAPK pathway inhibitionMultiple tumor typesStable diseaseEscalation studyPartial responseOral inhibitorPharmacodynamic effects
2018
A phase I study of AL101, a pan-NOTCH inhibitor, in patients (pts) with locally advanced or metastatic solid tumors.
El-Khoueiry A, Desai J, Iyer S, Gadgeel S, Ramalingam S, Horn L, LoRusso P, Bajaj G, Kollia G, Qi Z, Basak S, Fischer B, Davis M, Bedard P. A phase I study of AL101, a pan-NOTCH inhibitor, in patients (pts) with locally advanced or metastatic solid tumors. Journal Of Clinical Oncology 2018, 36: 2515-2515. DOI: 10.1200/jco.2018.36.15_suppl.2515.Peer-Reviewed Original Research
2017
A call for global harmonization of phase I oncology trials: Results from two parallel, first-in-human phase I studies of DS-7423, an oral PI3K/mTOR dual inhibitor in advanced solid tumors conducted in the United States and Japan.
Yokota T, Bendell J, LoRusso P, Tsushima T, Desai V, Kenmotsu H, Watanabe J, Ono A, Murugesan B, Silva J, Naito T, Greenberg J, Kumar P, Wang Y, Jikoh T, Shiga R, Ho A, Gounder M. A call for global harmonization of phase I oncology trials: Results from two parallel, first-in-human phase I studies of DS-7423, an oral PI3K/mTOR dual inhibitor in advanced solid tumors conducted in the United States and Japan. Journal Of Clinical Oncology 2017, 35: 2536-2536. DOI: 10.1200/jco.2017.35.15_suppl.2536.Peer-Reviewed Original ResearchMaximum-tolerated doseBody mass indexAdvanced solid tumorsBody weightPhase IFrequent treatment-related adverse eventsSolid tumorsNon-small cell lung cancerGrade 3 lung infectionHuman Phase I StudyTreatment-related adverse eventsCorresponding phase IGrade 3 dehydrationGrade 3 fatigueGrade 3 stomatitisGrade 4 hyperglycemiaPhase 2 doseGrade 3 rashCell lung cancerPhase I studiesSquamous cell carcinomaPI3K/mTOR dual inhibitorPI3K/mTORMTOR dual inhibitorStable disease
2016
18 A first-in-human phase I study to evaluate the ERK1/2 inhibitor GDC-0994 in patients with advanced solid tumors
Varga A, Soria J, Hollebecque A, LoRusso P, Vaishampayan U, Okrah K, Huang S, Murray E, Sanabria-Bohorquez S, Tagen M, Dokainish H, Mueller L, Burris H. 18 A first-in-human phase I study to evaluate the ERK1/2 inhibitor GDC-0994 in patients with advanced solid tumors. European Journal Of Cancer 2016, 69: s11. DOI: 10.1016/s0959-8049(16)32624-7.Peer-Reviewed Original ResearchAntibody–Drug Conjugates (ADCs) in Clinical Development
McLaughlin J, LoRusso P. Antibody–Drug Conjugates (ADCs) in Clinical Development. 2016, 321-344. DOI: 10.1002/9781119060727.ch13.Peer-Reviewed Original ResearchAntibody-drug conjugatesCytotoxic agentsMonoclonal antibodiesLocal immune responseFavorable safety profileConventional cytotoxic chemotherapyConventional cytotoxic agentsDifferent antibody–drug conjugatesImmune-stimulating agentsAnti-neoplastic agentsCytotoxic chemotherapySafety profileCancer patientsIL-2Clinical trialsImmune responseClinical developmentOncologist's abilityImproved efficacyPhase IDrug conjugatesAntibodiesEfficacyTarget effectsToxicity357O A phase I study evaluating DLYE5953A, an antibody-drug conjugate targeting the tumor-associated antigen lymphocyte antigen 6 complex locus E (Ly6E), in patients (Pts) with solid tumors
Modi S, Eder J, Lorusso P, Weekes C, Chandarlapaty S, Tolaney S, McLaughlin J, Camidge D, Chang C, Nazzal D, Chen S, Schuth E, Brunstein F, Darbonne W, Flanagan W, Ungewickell A, Shapiro G. 357O A phase I study evaluating DLYE5953A, an antibody-drug conjugate targeting the tumor-associated antigen lymphocyte antigen 6 complex locus E (Ly6E), in patients (Pts) with solid tumors. Annals Of Oncology 2016, 27: vi114. DOI: 10.1093/annonc/mdw368.01.Peer-Reviewed Original ResearchA phase I study of continuous (Con) and intermittent (Int) AZD2014 plus fulvestrant (F) in patients (pts) with estrogen receptor (ER+) metastatic breast cancer (BC).
Hamilton E, Patel M, Gluck W, Weise A, Pant S, Jones S, LoRusso P, Kittaneh M, Cosulich S, Harrington E, Littlewood G, Oelmann E, Burris H. A phase I study of continuous (Con) and intermittent (Int) AZD2014 plus fulvestrant (F) in patients (pts) with estrogen receptor (ER+) metastatic breast cancer (BC). Journal Of Clinical Oncology 2016, 34: 563-563. DOI: 10.1200/jco.2016.34.15_suppl.563.Peer-Reviewed Original Research
2014
2 Safety and early evidence of activity of a first-in-human phase I study of the novel cancer stem cell (CSC) targeting antibody OMP-52M51 (anti-Notch1) administered intravenously to patients with certain advanced solid tumors
Patnaik A, LoRusso P, Munster P, Tolcher A, Davis S, Heymach J, Ferraroto R, Xu L, Kapoun A, Faoro L, Lewicki J, Dupont J, Eckhardt S. 2 Safety and early evidence of activity of a first-in-human phase I study of the novel cancer stem cell (CSC) targeting antibody OMP-52M51 (anti-Notch1) administered intravenously to patients with certain advanced solid tumors. European Journal Of Cancer 2014, 50: 7. DOI: 10.1016/s0959-8049(14)70128-5.Peer-Reviewed Original ResearchEarly phase I study of the PARP inhibitor veliparib (ABT-888) alone or in combination with carboplatin/paclitaxel (CP) in patients with varying degrees of hepatic or renal dysfunction: A study of the NCI-Organ Dysfunction Working Group (ODG).
Tawbi H, Chu E, Lin Y, Hyman D, Goel S, Rudek M, Dowlati A, LoRusso P, Mulkerin D, Chew H, Kiesel B, Pollice L, Appleman L, Puhalla S, Stoller R, Lee J, Ivy P, Beumer J. Early phase I study of the PARP inhibitor veliparib (ABT-888) alone or in combination with carboplatin/paclitaxel (CP) in patients with varying degrees of hepatic or renal dysfunction: A study of the NCI-Organ Dysfunction Working Group (ODG). Journal Of Clinical Oncology 2014, 32: 2572-2572. DOI: 10.1200/jco.2014.32.15_suppl.2572.Peer-Reviewed Original ResearchVismodegib in the treatment of patients with metastatic basal cell carcinoma (mBCC) and distant metastases: Survival in the pivotal phase II and phase I studies.
Lewis K, Sekulic A, Hauschild A, Migden M, Oro A, LoRusso P, Rudin C, Dirix L, Solomon J, Hainsworth J, Williams S, Hou J, Von Hoff D. Vismodegib in the treatment of patients with metastatic basal cell carcinoma (mBCC) and distant metastases: Survival in the pivotal phase II and phase I studies. Journal Of Clinical Oncology 2014, 32: 9012-9012. DOI: 10.1200/jco.2014.32.15_suppl.9012.Peer-Reviewed Original ResearchPhase I and IIa studies of simtuzumab alone and in combination with FOLFIRI in patients with advanced solid tumors.
LoRusso P, Hecht J, Thai D, Hawkins M, Dong H, Tolcher A. Phase I and IIa studies of simtuzumab alone and in combination with FOLFIRI in patients with advanced solid tumors. Journal Of Clinical Oncology 2014, 32: 554-554. DOI: 10.1200/jco.2014.32.3_suppl.554.Peer-Reviewed Original ResearchTreatment-emergent AEsAdvanced solid tumorsColorectal cancerDose expansionIIa studyPhase ISolid tumorsCommon treatment-emergent AEsKRAS-mutant colorectal cancerDrug-related SAEsPhase II studyPhase IIa trialPhase IIa studyMutant colorectal cancerExtracellular matrix enzymesMedian PFSIIa trialUnacceptable toxicityEscalation studyII studyDose escalationFourth dosesTumor sizePancreatic neuroendocrinePromising efficacy
2013
Predictive value of phase I trials for safety and final approved dose in later trials: Analysis of 33,845 patients.
Fontes Jardim D, Hess K, LoRusso P, Kurzrock R, Hong D. Predictive value of phase I trials for safety and final approved dose in later trials: Analysis of 33,845 patients. Journal Of Clinical Oncology 2013, 31: 2509-2509. DOI: 10.1200/jco.2013.31.15_suppl.2509.Peer-Reviewed Original ResearchDose-limiting toxicityMultiple logistic regression analysisDeath rateLater trialsPhase IPhase II doseRelevant side effectsDose of agentDrug Administration websiteLogistic regression analysisChi-squared testAdverse eventsMultivariable analysisSafety profileFinal doseGrade 3Oral drugsNew agentsSide effectsPackage insertsPredictive valueUS FoodRegistration trialsCytotoxic agentsSignificant toxicityPhase I, first-in-human, open-label, dose-escalation study of U3-1565, a fully human anti-HB-EGF monoclonal antibody, in patients with advanced solid tumors.
Moore K, Bendell J, Olszanski A, Desai M, Jansen M, Scheyer R, Senaldi G, LoRusso P. Phase I, first-in-human, open-label, dose-escalation study of U3-1565, a fully human anti-HB-EGF monoclonal antibody, in patients with advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2519-2519. DOI: 10.1200/jco.2013.31.15_suppl.2519.Peer-Reviewed Original ResearchAdvanced solid tumorsYear old femaleAnti-tumor activitySolid tumorsMonoclonal antibodiesDose level cohortsDose-expansion studyDose-escalation studyBi-exponential dispositionEpidermal growth factor-like growth factorEGF family membersTumor growth inhibitionFactor-like growth factorG1 toxicityProgressive diseaseAnti-angiogenesis activityStandard treatmentPatientsRelated AEsExtension phasePhase IGrowth factorLevel cohortsWeeksWeekly