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 timeA phase 2 study of the WEE1 inhibitor AZD1775 in SETD2-deficient advanced solid tumor malignancies.
Maldonado E, Rathmell W, Shapiro G, Rodon Ahnert J, Mahalingam D, Trikalinos N, Rezazadeh A, Adorno Febles V, Parikh M, Boerner S, Krings G, Takebe N, LoRusso P, Aggarwal R. A phase 2 study of the WEE1 inhibitor AZD1775 in SETD2-deficient advanced solid tumor malignancies. Journal Of Clinical Oncology 2023, 41: 3104-3104. DOI: 10.1200/jco.2023.41.16_suppl.3104.Peer-Reviewed Original ResearchClear cell renal cell carcinomaSolid tumor malignanciesClinical benefit rateObjective response rateDuration of responseTumor malignancyEvaluable ptsStable diseaseObjective responseAdverse eventsTumor regressionMetastatic clear cell renal cell carcinomaAdvanced solid tumor malignanciesMetastatic solid tumor malignanciesCommon adverse eventsDurable stable diseaseECOG PS 0RECIST 1.1 criteriaSubset of ptsPhase 2 studyCohort of patientsCell renal cell carcinomaNext-generation sequencing panelBest overall responseRenal cell carcinomaMirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose expansion results.
Carneiro B, Perets R, Dowlati A, LoRusso P, Yonemori K, He L, Munasinghe W, Noorani B, Johnson E, Zugazagoitia J. Mirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose expansion results. Journal Of Clinical Oncology 2023, 41: 3027-3027. DOI: 10.1200/jco.2023.41.16_suppl.3027.Peer-Reviewed Original ResearchNon-small cell lung cancerSmall cell lung cancerOverall response rateCommon adverse eventsRefractory solid tumorsCell lung cancerSCLC cohortBest overall responseAdverse eventsMonotherapy cohortTaxane therapyLung cancerSolid tumorsConfirmed overall response rateDose-expansion phaseOngoing phase 1Phase 2 dosePrior taxane therapyTolerable safety profileDisease control rateGrade 3/4 neutropeniaOpen-label studyDose-escalation phasePhase 1 studySingle-agent activity
2021
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
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 boardClinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation
Kim J, Cardin DB, Vaishampayan UN, Kato S, Grossman SR, Glazer P, Shyr Y, Ivy SP, LoRusso P. Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. The Oncologist 2021, 26: e1104-e1109. PMID: 33742489, PMCID: PMC8265343, DOI: 10.1002/onco.13758.Peer-Reviewed Original ResearchConceptsMetastatic pancreatic adenocarcinomaHomologous recombination DNA repair deficiencyMetastatic pancreatic ductal adenocarcinomaPancreatic ductal adenocarcinomaOlaparib combinationStable diseaseBRCA mutationsAdverse eventsDuctal adenocarcinomaCommon treatment-related adverse eventsVascular endothelial growth factor receptor inhibitorEndothelial growth factor receptor inhibitorTreatment-related adverse eventsGrowth factor receptor inhibitorsPrior systemic chemotherapyMedian overall survivalObjective response rateGermline BRCA mutationsBest overall responseExpression of BRCA1/2Restaging scanCancer cell linesPrimary endpointStudy drugSystemic chemotherapy
2020
A 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
2012
Phase Ib study of CNTO 888 (anti-CCL 2) in combination with chemotherapies for treatment of patients with solid tumors.
Calles A, Brana I, LoRusso P, Yee L, Puchalski T, Seetharam S, Balvers M, De Boer C, Elsayed Y, Calvo E, Tabernero J. Phase Ib study of CNTO 888 (anti-CCL 2) in combination with chemotherapies for treatment of patients with solid tumors. Journal Of Clinical Oncology 2012, 30: 3059-3059. DOI: 10.1200/jco.2012.30.15_suppl.3059.Peer-Reviewed Original ResearchCC chemokine ligand 2Adverse eventsPartial responseArm 1Febrile neutropeniaArm 3Arm 2Arm 4PK profilesGrade 4 febrile neutropeniaGrade 3 neutropeniaPhase Ib studySerious adverse eventsTreatment of patientsBest overall responsePreclinical antitumor activityCEC countsGemcitabine 1000Prior chemotherapyStable diseaseAdvanced diseaseObjective responseStandard chemotherapySurgical resectionHr post treatment