2024
Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors
Choi Y, Dharia N, Jun T, Chang J, Royer-Joo S, Yau K, Assaf Z, Aimi J, Sivakumar S, Montesion M, Sacher A, LoRusso P, Desai J, Schutzman J, Shi Z, group A. Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors. Clinical Cancer Research 2024, 30: of1-of10. PMID: 38995268, PMCID: PMC11369623, DOI: 10.1158/1078-0432.ccr-24-0255.Peer-Reviewed Original ResearchConceptsKRAS G12C mutationTumor fractionSolid tumorsTumor typesG12C mutationOn-treatment time pointsNon-small cell lung cancerMutational heterogeneityAssociated with tumor typeProgression-free survivalPlasma samplesPhase 1 studyCell lung cancerCycle 1 dayAssociated with patient outcomesVariant allele frequencyAssociated with responseCtDNA levelsCtDNA profilingMetastatic sitesTruncal mutationsTumor DNATreatment responseLung cancerTumor tissuesCirculating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors
Hu Y, Narayan A, Xu Y, Wolfe J, Vu D, Trinh T, Kantak C, Ivy S, Eder J, Deng Y, LoRusso P, Kim J, Patel A. Circulating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors. JCO Precision Oncology 2024, 8: e2300289. PMID: 38412387, PMCID: PMC10914240, DOI: 10.1200/po.23.00289.Peer-Reviewed Original ResearchConceptsCell-free circulating tumor DNANon-small-cell lung cancerSmall-cell lung cancerTriple-negative breast cancerPancreatic ductal adenocarcinomaAdvanced solid tumorsVariant allele fractionRadiographic responseOverall survivalCombination therapySolid tumorsCtDNA levelsLung cancerPretreated advanced solid tumorsDays of combination therapyMetastatic pancreatic ductal adenocarcinomaResponse to anticancer therapyAssociated with disease progressionProgression-free survivalPlasma samplesLead-inPoly(ADP-riboseInferior OSTumor DNASurvival outcomes
2023
Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors
Kim T, Bedard P, LoRusso P, Gordon M, Bendell J, Oh D, Ahn M, Garralda E, D’Angelo S, Desai J, Hodi F, Wainberg Z, Delord J, Cassier P, Cervantes A, Gil-Martin M, Wu B, Patil N, Jin Y, Hoang T, Mendus D, Wen X, Meng R, Cho B. Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors. JAMA Oncology 2023, 9: 1574-1582. PMID: 37768658, PMCID: PMC10540058, DOI: 10.1001/jamaoncol.2023.3867.Peer-Reviewed Original ResearchConceptsObjective response rateAdvanced solid tumorsAdverse eventsPhase 1bAntitumor activityCancer cohortNon-small cell lung cancer (NSCLC) cohortFrequent treatment-related adverse eventsInvestigator-assessed objective response rateSolid tumorsCell lung cancer cohortTreatment-related adverse eventsMajority of AEsEnd pointClinical cutoff dateDose-escalation cohortsDose-expansion cohortsEsophageal cancer cohortPhase 2 dosePrior cancer therapyPrimary end pointSecondary end pointsHalf of patientsNew safety signalsAntitumor immune responseSingle-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Sacher A, LoRusso P, Patel M, Miller W, Garralda E, Forster M, Santoro A, Falcon A, Kim T, Paz-Ares L, Bowyer S, de Miguel M, Han S, Krebs M, Lee J, Cheng M, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Dharia N, Schutzman J, Desai J. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. New England Journal Of Medicine 2023, 389: 710-721. PMID: 37611121, DOI: 10.1056/nejmoa2303810.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAntineoplastic AgentsCarcinoma, Non-Small-Cell LungColorectal NeoplasmsEnzyme InhibitorsHumansLung NeoplasmsMutationProto-Oncogene Proteins p21(ras)ConceptsMedian progression-free survivalTreatment-related adverse eventsProgression-free survivalAdverse eventsSolid tumorsG12C mutationLow-grade adverse eventsGrade 3 eventsGrade 4 eventsTreatment-related deathsDiscontinuation of treatmentMetastatic solid tumorsPhase 1 studyDurable clinical responsesBiomarkers of responseKRAS G12C mutationAssessment of safetyVariant allele frequencyClinical responseColorectal cancerSerial assessmentDose reductionG12C inhibitorsPatientsTumor DNAFirst-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors
Bendell J, LoRusso P, Overman M, Noonan A, Kim D, Strickler J, Kim S, Clarke S, George T, Grimison P, Barve M, Amin M, Desai J, Wise-Draper T, Eck S, Jiang Y, Khan A, Wu Y, Martin P, Cooper Z, Elgeioushi N, Mueller N, Kumar R, Patel S. First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. Cancer Immunology, Immunotherapy 2023, 72: 2443-2458. PMID: 37016126, PMCID: PMC10264501, DOI: 10.1007/s00262-023-03430-6.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Non-Small-Cell LungFatigueHumansLung NeoplasmsConceptsTreatment-related adverse eventsPancreatic ductal adenocarcinomaColorectal cancerExpansion cohortHuman studiesResponse rateAnti-CD73 monoclonal antibodyProgression-free survival ratesTumor cellsMonoclonal antibodiesCommon being fatigueManageable safety profileObjective response rateAdvanced colorectal cancerAdvanced solid tumorsCell lung cancerPeripheral T cellsDate of registrationCD73 enzymatic activityAdverse eventsEscalation cohortsLocal immunosuppressionCD73 expressionSafety profileLung cancer
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 ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCD4-Positive T-LymphocytesHumansInducible T-Cell Co-Stimulator ProteinLung NeoplasmsNivolumabProspective StudiesConceptsSubset 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