2024
First-in-human phase I trial of the oral first-in-class ubiquitin specific peptidase 1 (USP1) inhibitor KSQ-4279 (KSQi), given as single agent (SA) and in combination with olaparib (OLA) or carboplatin (CARBO) in patients (pts) with advanced solid tumors, enriched for deleterious homologous recombination repair (HRR) mutations.
Yap T, Lakhani N, Patnaik A, Lee E, Gutierrez M, Moore K, Carneiro B, Hays J, Huang M, LoRusso P, Wylie A, Cadzow L, Goulet M, Tobin E, Krieter O, Schmid D, Blake S, Dieterich M, Jamois C, Harris P. First-in-human phase I trial of the oral first-in-class ubiquitin specific peptidase 1 (USP1) inhibitor KSQ-4279 (KSQi), given as single agent (SA) and in combination with olaparib (OLA) or carboplatin (CARBO) in patients (pts) with advanced solid tumors, enriched for deleterious homologous recombination repair (HRR) mutations. Journal Of Clinical Oncology 2024, 42: 3005-3005. DOI: 10.1200/jco.2024.42.16_suppl.3005.Peer-Reviewed Original ResearchUbiquitin specific peptidase 1Treatment-emergent adverse eventsHomologous recombination repair mutationsSingle agentPARP inhibitorsHomologous recombination repairFirst-in-human phase I trialPreliminary anti-tumor activityPaired tumor biopsiesTNBC PDX modelsDisease control ratePhase I trialAUC 4Olaparib concentrationsRECIST PRDose escalationExpansion cohortCancer ptsDose proportionalityTumor biopsiesI trialMaculopapular rashPDX modelsDiscontinued treatmentDNA damage response pathway
2009
A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors
Wagner A, Von Hoff D, LoRusso P, Tibes R, Mazina K, Ware J, Yan Y, Derynck M, Demetri G. A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors. Journal Of Clinical Oncology 2009, 27: 3501-3501. DOI: 10.1200/jco.2009.27.15_suppl.3501.Peer-Reviewed Original ResearchDose-proportional increaseAnti-tumor activityDose levelsPK dataPan-PI3K inhibitor GDCSolid tumorsPhase ICA-125 responseDose escalation armDose-escalation cohortsDrug-related AEsGrade 1/2 nauseaPreliminary PK dataSingle-dose PKAdvanced solid tumorsTotal daily dosesFDG-PET uptakeSelective oral inhibitorSteady-state PKHuman phase IProstate cancer modelPotential signsBID armCancer ptsQD arm