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
2023
First-in-human phase 1 dose escalation study of the KAT6 inhibitor PF-07248144 in patients with advanced solid tumors.
Sommerhalder D, Hamilton E, Mukohara T, Yonemori K, Mita M, Yamashita T, Zheng J, Liu L, Maity A, Homji Mishra N, Bogg O, Li M, LoRusso P. First-in-human phase 1 dose escalation study of the KAT6 inhibitor PF-07248144 in patients with advanced solid tumors. Journal Of Clinical Oncology 2023, 41: 1054-1054. DOI: 10.1200/jco.2023.41.16_suppl.1054.Peer-Reviewed Original ResearchWhite blood cellsEndocrine therapyPartial responsePart 1BPhase 1 dose-escalation studyHuman phase 1 studyPreclinical anti-tumor activityDurable partial responseTreatment-related AEsAdvanced solid tumorsDose-escalation studySystemic anticancer therapyPhase 1 studyAnti-tumor activityPart 1AEscalation studyMedian agePrior linesStandard therapyDose escalationCDK4/6 inhibitorsDisease progressionBreast cancerTumor biopsiesG1-2
2021
866 RBN-2397, a novel, potent, and selective PARP7 inhibitor, induces tumor-intrinsic type I interferon responses and adaptive immunity in preclinical models and patient tumors
Kuplast-Barr K, Kuplast-Barr K, Johnson M, Patel M, Yap T, Falchook G, LoRusso P, Abo R, Liu C, Manyak E, Cleary L, Bozon V, Parasuraman S, Keilhack H, McEachern K. 866 RBN-2397, a novel, potent, and selective PARP7 inhibitor, induces tumor-intrinsic type I interferon responses and adaptive immunity in preclinical models and patient tumors. Journal For ImmunoTherapy Of Cancer 2021, 9: a907-a907. DOI: 10.1136/jitc-2021-sitc2021.866.Peer-Reviewed Original ResearchPreclinical modelsPatient tumor biopsiesTumor biopsiesAdaptive immunityCancer cellsHuman phase 1 studyTumor-specific immune memoryCD8 T cell infiltrationTumor microenvironmentPhase I clinical studyType IAdvanced solid tumorsPhase 1 studyT cell infiltrationGranzyme B expressionDurable tumor regressionAdaptive immune responsesInterferon-stimulated gene expressionImmune stimulatory effectsType I interferon responseCytosolic nucleic acidsType I interferonActivated T cellsNon-tumor tissuesI interferon response
2020
Pharmacodynamic effects in blood and tumor tissue of eftozanermin alfa, a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist.
Motwani M, Modi D, Penugonda S, Zhang C, Palma J, Cunningham A, Calvo E, de Jonge M, LoRusso P. Pharmacodynamic effects in blood and tumor tissue of eftozanermin alfa, a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist. Journal Of Clinical Oncology 2020, 38: e15668-e15668. DOI: 10.1200/jco.2020.38.15_suppl.e15668.Peer-Reviewed Original ResearchPharmacodynamic effectsReceptor agonistMultiplex immunohistochemistryKRAS-mutant colorectal cancerTumor tissueDose-expansion cohortsSimilar time pointsMutant allele fractionM65 levelsH postdoseColorectal cancerPost-TxDownstream pathway activationPancreatic cancerHematologic malignanciesLiver enzymesScreening periodReverse phase protein arrayBiopsy coresTumor biopsiesMutant allele frequencyBiopsy samplesDose levelsBiopsyTumor typesA phase I study of ALX148, a CD47 blocker, in combination with standard anticancer antibodies and chemotherapy regimens in patients with advanced malignancy.
Chow L, Gainor J, Lakhani N, Lee K, Chung H, Lee J, LoRusso P, Bang Y, Hodi F, Santana-Davila R, Fanning P, Squifflet P, Jin F, Wan H, Kuo T, Pons J, Randolph S, Messersmith W. A phase I study of ALX148, a CD47 blocker, in combination with standard anticancer antibodies and chemotherapy regimens in patients with advanced malignancy. Journal Of Clinical Oncology 2020, 38: 3056-3056. DOI: 10.1200/jco.2020.38.15_suppl.3056.Peer-Reviewed Original ResearchAdverse eventsCheckpoint inhibitorsData cutoffAdvanced malignanciesImmune responseNeck squamous cell cancerCommon being fatigueSquamous cell cancerStandard chemotherapy regimensAdaptive immune responsesHost immune responseAnti-cancer antibodiesCombination cohortAdvanced diseaseChemotherapy regimensGastroesophageal cancerStandard chemotherapyCell cancerPlatinum therapyExcellent tolerabilityHistoric controlsPharmacodynamic markersImmune cellsClinical activityTumor biopsiesAssociation of an RNA signature (RS) with emergence of ICOS hi CD4 T cells and efficacy outcomes for the ICOS agonist vopratelimab (vopra) and nivolumab (nivo) in patients (pts) on the ICONIC trial.
Yap T, Gainor J, Burris H, Kummar S, Pachynski R, Callahan M, LoRusso P, Tykodi S, Gibney G, Falchook G, Rahma O, Seiwert T, Papadopoulos K, Mier J, Hashambhoy-Ramsay Y, Felitsky D, Lee D, McGrath L, Harvey C, Hooper E. Association of an RNA signature (RS) with emergence of ICOS hi CD4 T cells and efficacy outcomes for the ICOS agonist vopratelimab (vopra) and nivolumab (nivo) in patients (pts) on the ICONIC trial. Journal Of Clinical Oncology 2020, 38: 14-14. DOI: 10.1200/jco.2020.38.5_suppl.14.Peer-Reviewed Original ResearchCD4 T cellsCD4 T effector cellsT effector cellsT cellsRNA signatureRECIST responseClinical outcomesEffector cellsTumor biopsiesPre-treatment tumor biopsiesCD4 T cell populationBaseline tumor biopsiesPD-L1 TPSPD-1 inhibitorsAdvanced solid tumorsRetrospective subset analysisImmune cell infiltrationPotential predictive biomarkersT cell populationsPD-L1 IHCActivated T cellsBaseline tumorEfficacy outcomesPD-L1Combo therapy
2012
Targeting hyaluronan (HA) in tumor stroma: A phase I study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of pegylated hyaluronidase (PEGPH20) in patients with solid tumors.
Borad M, Ramanathan R, Bessudo A, LoRusso P, Shepard H, Maneval D, Jiang P, Zhu J, Frost G, Infante J. Targeting hyaluronan (HA) in tumor stroma: A phase I study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of pegylated hyaluronidase (PEGPH20) in patients with solid tumors. Journal Of Clinical Oncology 2012, 30: 2579-2579. DOI: 10.1200/jco.2012.30.15_suppl.2579.Peer-Reviewed Original ResearchMusculoskeletal eventsSolid tumorsFDG-PETDCE-MRITumor biopsiesTumor perfusionInterstitial fluid pressureOngoing phase 1 studiesTreatment-refractory solid tumorsWeekly dosing scheduleDose limiting toxicitiesPhase 1 studyWeeks of dosingEfficacy of chemotherapyTerminal half lifeFDG-PET imagesOral dexamethasoneTumor hyaluronanCytotoxic chemotherapyMost patientsDosing schedulesLimiting toxicitiesPoor prognosisSystemic exposureHA depletion
2007
Phase I experience with c-MET inhibitor XL880 administered orally to patients (pts) with solid tumors
Eder J, Heath E, Appleman L, Shapiro G, Wang D, Malburg L, Zhu A, Leader T, Wolanski A, LoRusso P. Phase I experience with c-MET inhibitor XL880 administered orally to patients (pts) with solid tumors. Journal Of Clinical Oncology 2007, 25: 3526-3526. DOI: 10.1200/jco.2007.25.18_suppl.3526.Peer-Reviewed Original ResearchStable diseaseTumor biopsiesPhase ITreatment tumor biopsiesCommon adverse eventsECOG performance statusPhase II trialPhase 1 studyCorrelative studiesHepatocyte growth factor receptorInhibition of PDGFRβAdequate liverEvaluable ptsGrowth factor receptorII trialRECIST criteriaAdverse eventsBrain metastasesHepatic transaminasesPartial responsePerformance statusRenal functionDaily dosePlasma markersNeck cancer