2022
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
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
516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial
Aix S, Calvo E, Moreno V, Garralda E, Cervantes A, Ramalingam S, Pérez J, LoRusso P, Furqan M, Cho D, Muik A, Lagkadinou E, Türeci Ö, Couto S, Pencheva N, Forssmann U, Şahin U, Ahmadi T, Higgs B, Jure-Kunkel M, Melero I. 516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial. Journal For ImmunoTherapy Of Cancer 2021, 9: a546-a546. DOI: 10.1136/jitc-2021-sitc2021.516.Peer-Reviewed Original ResearchPrior anti-PD-1 therapyAnti-PD-1 therapyPD-L1NK cellsTumor reductionAnti-PD-1 combination therapyEffector memory T cellsPD-L1 blockadePhase 1/2a trialPrior systemic therapySoluble immune mediatorsTumor PD-L1Disease control rateAdvanced solid tumorsAntitumor immune responseSubset of patientsMemory T cellsSerial blood samplesImproved clinical efficacyTumor biopsy specimensCycle 1Tumor biopsy samplesEthics committees/institutional review boardsInstitutional review boardCycle 2Clinical pharmacokinetics of bdtx-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study.
Waters N, Patel M, Schram A, Ahnert J, Jauhari S, Sachdev J, Zhu V, LoRusso P, Nguyen D, Hong D, Tarilonte L, Humphrey R, Janne P, Hamilton E, Witt K. Clinical pharmacokinetics of bdtx-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study. Journal Of Clinical Oncology 2021, 39: 3097-3097. DOI: 10.1200/jco.2021.39.15_suppl.3097.Peer-Reviewed Original ResearchHigh-fat mealFasted stateEGFR WTRapid absorptionPK/PD profilesDose-escalation cohortsNon-fasting statePhase 2 doseAdvanced solid malignanciesHigh-fat breakfastSubset of patientsElimination t 1/2Serial blood samplesNon-compartmental methodsDose-dependent increaseSustained pharmacodynamic effectsMedian tmaxEscalation cohortsCrossover fashionDose escalationFat mealPharmacodynamic effectsSystemic exposureMultiple dosesClinical Pharmacokinetics
2020
Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti–c-Met Antibody, in Patients with Advanced Solid Tumors
Strickler JH, LoRusso P, Salgia R, Kang YK, Yen C, Lin CC, Ansell P, Motwani M, Wong S, Yue H, Wang L, Reilly E, Afar D, Naumovski L, Ramanathan RK. Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti–c-Met Antibody, in Patients with Advanced Solid Tumors. Molecular Cancer Therapeutics 2020, 19: 1210-1217. PMID: 32127466, DOI: 10.1158/1535-7163.mct-19-0529.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsSolid tumorsStable diseaseDose escalationCommon treatment-related adverse eventsAnti-c-Met antibodyTreatment-related adverse eventsDose-expansion phaseI Dose-EscalationAcceptable safety profileResponse Evaluation CriteriaDose-limiting toxicitySubset of patientsLinear pharmacokinetic profilePeak plasma concentrationAcute infusion reactionsHuman phase IDose cohortsDose expansionRECIST criteriaAdverse eventsEscalation cohortsInfusion reactionsObjective responsePartial response