2020
412 First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors
Garralda E, Geva R, Ben-Ami E, Maurice-Dror C, Calvo E, LoRusso P, Türeci Ö, Niewood M, Şahin U, Jure-Kunkel M, Forssmann U, Ahmadi T, Melero I. 412 First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors. Journal For ImmunoTherapy Of Cancer 2020, 8: a250-a251. DOI: 10.1136/jitc-2020-sitc2020.0412.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-limiting toxicityPhase I/IIa trialTransaminase elevationAdverse eventsSolid tumorsIIa trialClinical activityT cellsDose levelsGrade 3 transaminase elevationTreatment-related adverse eventsEffector memory T cellsSerum interferon-gamma levelTriple-negative breast cancerInitial clinical activityAntitumor activityImmune checkpoint inhibitorsManageable safety profilePD-L1 axisInterferon-gamma levelsMemory T cellsEarly clinical activityEnd of infusionNarrow therapeutic window
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 activityA phase Ia study of CC-90003, a selective extracellular signal-regulated kinase (ERK) inhibitor, in patients with relapsed or refractory BRAF or RAS-mutant tumors.
Mita M, LoRusso P, McArthur G, Kim E, Bray G, Hock N, Laille E, Aronchik I, Filvaroff E, Wu X, Bendell J. A phase Ia study of CC-90003, a selective extracellular signal-regulated kinase (ERK) inhibitor, in patients with relapsed or refractory BRAF or RAS-mutant tumors. Journal Of Clinical Oncology 2017, 35: 2577-2577. DOI: 10.1200/jco.2017.35.15_suppl.2577.Peer-Reviewed Original ResearchBRAF-mutant tumorsObjective responsePK parametersMutant tumorsDose reduction/interruptionGrade 3 transaminase elevationPeripheral blood mononuclear cellsPhase Ia studyReduction/interruptionBlood mononuclear cellsExtracellular signal-regulated kinase (ERK) inhibitorSignal-regulated kinase inhibitorPotent anti-proliferative activityRECIST 1.1Transaminase elevationNeurologic toxicityNineteen patientsMononuclear cellsMultiple dosesRAS mutant tumorsHuman studiesPatientsPK profilesAnti-proliferative activityGrade 1
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