2024
223P Tumor whole genome sequencing-based ultrasensitive ctDNA analysis as an early biomarker for clinical outcome in immune checkpoint inhibitor (ICI) phase I clinical trials (Ph1) and a tool for beyond progressive disease by iRECIST
Toledo R, García A, Moreno A, Mirallas O, Galvao V, Casal G, Vieito M, Braña I, Oberoi A, Bardaji M, Keough K, Navarro F, Jimenez J, Olano A, Nuciforo P, Abbott C, Pugh J, Chen R, Boyle S, Garralda E. 223P Tumor whole genome sequencing-based ultrasensitive ctDNA analysis as an early biomarker for clinical outcome in immune checkpoint inhibitor (ICI) phase I clinical trials (Ph1) and a tool for beyond progressive disease by iRECIST. Annals Of Oncology 2024, 35: s304-s305. DOI: 10.1016/j.annonc.2024.08.2227.Peer-Reviewed Original Research77 Impact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC)
Dizman N, Ebrahimi H, Barragan-Carrillo R, Meza L, Bergerot P, Dorff T, BSc J, Zengin Z, Castro D, Chehrazi-Raffle A, Triphathi A, Trent J, Takahashi M, Oka K, Higashi S, Caporaso G, Lee K, Pal S. 77 Impact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC). The Oncologist 2024, 29: s5-s5. PMCID: PMC11301884, DOI: 10.1093/oncolo/oyae181.007.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsStandard of careGut microbiome compositionStandard of care cohortMicrobiome compositionGut dysbiosisClinical outcomesClinically relevant microbial speciesCompared gut microbiome diversityCell metastatic renal cell carcinomaRandomized phase I clinical trialClinically relevant speciesAssociated with ICI responseStandard of care regimensRelevant microbial speciesGut microbiome diversityRatio of Firmicutes/BacteroidetesPhase I clinical trialPhase III studyBaseline to weekAnalyzed stool samplesFirst-line treatmentRenal cell carcinomaBeta diversityImpact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC).
Dizman N, Ebrahimi H, Barragán Carrillo R, Meza L, Bergerot P, Dorff T, Hsu J, Zengin Z, Castro D, Chehrazi-Raffle A, Tripathi A, Trent J, Takahashi M, Oka K, Higashi S, Caporaso G, Lee K, Pal S. Impact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2024, 42: 4550-4550. DOI: 10.1200/jco.2024.42.16_suppl.4550.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsStandard of careStandard of care cohortGut microbiome compositionMicrobiome compositionClinical outcomesCell metastatic renal cell carcinomaRandomized phase I clinical trialGut dysbiosisAssociated with ICI responseStandard of care regimensClinically relevant microbial speciesCompared gut microbiome diversityPhase I clinical trialClinically relevant speciesPhase III studyRelevant microbial speciesBaseline to weekFirst-line treatmentGut microbiome diversityRatio of Firmicutes/BacteroidetesRenal cell carcinomaWilcoxon matched pairs testAnalyzed stool samplesThe Right Dose: Results of a Patient Advocate–Led Survey of Individuals With Metastatic Breast Cancer Regarding Treatment-Related Side Effects and Views About Dosage Assessment to Optimize Quality of Life
Loeser A, Kim J, Peppercorn J, Burkard M, Niemierko A, Juric D, Kalinsky K, Rugo H, Glenn L, Hodgdon C, Maues J, Johnson S, Padron N, Parekh K, Lustberg M, Bardia A. The Right Dose: Results of a Patient Advocate–Led Survey of Individuals With Metastatic Breast Cancer Regarding Treatment-Related Side Effects and Views About Dosage Assessment to Optimize Quality of Life. JCO Oncology Practice 2024, 20: 972-983. PMID: 38518184, DOI: 10.1200/op.23.00539.Peer-Reviewed Original ResearchMetastatic breast cancerTreatment-related side effectsSide effectsDose reductionBreast cancerLow dosesQuality of lifePhase I clinical trialFlexible dosing optionsMaximum tolerated doseDose of drugCourse of therapyIndividual doses of drugsCourse of treatmentPatient-physician discussionsPrescribed doseTolerated doseTargeted therapyDosing optionsAlternative dosingMedical oncologistsDose initiationHigh dosesImprove patient well-beingEffective treatmentAbstract B026: Detection and characterization of DDR reversion alterations in baseline tissue and plasma samples from patients enrolled in the TRESR and ATTACC Phase I clinical trials
Silverman I, Schonhoft J, Jain E, Ulanet D, Yang J, Kim I, Fei K, Lagow E, Yablonovitch A, Cecchini M, Rosen E, Lee E, Lheureux S, Yap T, Fontana E, Koehler M, Rimkunas V. Abstract B026: Detection and characterization of DDR reversion alterations in baseline tissue and plasma samples from patients enrolled in the TRESR and ATTACC Phase I clinical trials. Cancer Research 2024, 84: b026-b026. DOI: 10.1158/1538-7445.dnarepair24-b026.Peer-Reviewed Original ResearchPoly(ADP-ribose) polymerase inhibitorsPhase I clinical trialDNA damage repairReversible alterationsECOG PS 0-1Baseline tissuePlatinum-based therapyPlasma samplesInterpretation of efficacy dataHRD-related genesDamage repairDDR alterationsTumor biopsiesOvarian cancerSingle nucleotide variantsWhole-genome sequencingDiagnostic challengeSolid tumorsClinical developmentEvaluate safetyEfficacy dataPolymerase inhibitorsTumorAtaxia telangiectasiaPatients
2023
NCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors
Cecchini M, Walther Z, Wei W, Hafez N, Pilat M, Boerner S, Durecki D, Eder J, Schalper K, Chen A, LoRusso P. NCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors. Cancer Research Communications 2023, 3: 1113-1117. PMID: 37377610, PMCID: PMC10292219, DOI: 10.1158/2767-9764.crc-22-0485.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityHomologous recombination deficiencyPARP inhibitorsStable diseaseWeekly irinotecanObjective responseDay 1Day 3Solid tumorsPhase I dose-escalation studyTwice daily days 1I dose-escalation studyPhase I clinical trialDaily days 1Dose level 1Doses of veliparibGrade 3 neutropeniaMultiple-dose schedulesProgression-free survivalAdvanced solid tumorsDose-escalation studyEvaluable patientsNonoverlapping toxicitiesDose scheduleSystemic treatmentAssessment of short-chain fatty acid (SCFA) and circulating cytokine trends in a clinical trial of nivolumab/ipilimumab and CBM588 in metastatic renal cell carcinoma (mRCC).
Dizman N, Pathak K, Alcantara M, Meza L, Bergerot P, Willey M, Dorff T, Hsu J, Zengin Z, Castro D, Ebrahimi H, Chehrazi-Raffle A, Tripathi A, Trent J, Takahashi M, Oka K, Higashi S, Kortylewski M, Pirrotte P, Pal S. Assessment of short-chain fatty acid (SCFA) and circulating cytokine trends in a clinical trial of nivolumab/ipilimumab and CBM588 in metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2023, 41: 4556-4556. DOI: 10.1200/jco.2023.41.16_suppl.4556.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaNivolumab/ipilimumabObjective response rateShort-chain fatty acidsPlasma short-chain fatty acidsImmune checkpoint blockadeCheckpoint blockadeCytokine levelsSCFA levelsClinical trialsRandomized phase I clinical trialSarcomatoid Metastatic Renal Cell CarcinomaPhase I clinical trialStool SCFA levelsAcid levelsTreatment-naïve patientsAltered amino acid metabolismRenal cell carcinomaIpilimumab armNaïve patientsButyric acid levelsSerum cytokinesClinical outcomesCell carcinomaBiologic rationaleClinical outcome and prognostic factors for Asian patients in Phase I clinical trials
Loh J, Wu J, Chieng J, Chan A, Yong W, Sundar R, Lee S, Wong A, Lim J, Tan D, Soo R, Goh B, Tai B, Chee C. Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials. British Journal Of Cancer 2023, 128: 1514-1520. PMID: 36797357, PMCID: PMC10070409, DOI: 10.1038/s41416-023-02193-2.Peer-Reviewed Original ResearchConceptsNeutrophil-lymphocyte ratioRoyal Marsden HospitalPhase I studyPhase I clinical trialPoor ECOG statusPre-treated patientsPrimary tumor sitePhase I populationLonger-term survivalECOG statusPrognostic factorsPrognostic scoreRetrospective reviewTumor siteAsian patientsSolid tumorsClinical outcomesPoor prognosisBackgroundPatient selectionPrognostic abilityPrognostic modelPatientsPrognosisIncreased scoresScores
2022
A phase I trial to evaluate the biologic effect of CBM588 (Clostridium butyricum) in combination with cabozantinib plus nivolumab for patients with metastatic renal cell carcinoma (mRCC).
Meza L, Malhotra J, Zengin Z, Dizman N, Hsu J, Chawla N, Chehrazi-Raffle A, Muddasani R, Govindarajan A, Castro D, Dorff T, Lyou Y, Frankel P, Pal S. A phase I trial to evaluate the biologic effect of CBM588 (Clostridium butyricum) in combination with cabozantinib plus nivolumab for patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2022, 40: tps4606-tps4606. DOI: 10.1200/jco.2022.40.16_suppl.tps4606.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaClinical responseClear cell metastatic renal cell carcinomaTyrosine kinase inhibitor cabozantinibBiologic effectsGut microbiomeImmune checkpoint inhibitor nivolumabOne-sided type I errorPhase I clinical trialFirst-line treatmentProgression-free survivalStudy's primary endpointCheckpoint inhibitor nivolumabPhase I trialPhase 1 trialSubgroup of patientsWeeks of treatmentCytokines/chemokinesDose/scheduleOngoing phase IRenal cell carcinomaImproved clinical benefitBifidobacterium sppEligible patientsPo bidNCI 9938: Phase I clinical trial of ATR inhibitor berzosertib (M6620, VX-970) in combination with irinotecan in patients with advanced solid tumors.
Villaruz L, Kelly K, Waqar S, Davis E, Shapiro G, LoRusso P, Dees E, Normolle D, Rhee J, Chu E, Gore S, Beumer J. NCI 9938: Phase I clinical trial of ATR inhibitor berzosertib (M6620, VX-970) in combination with irinotecan in patients with advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 3012-3012. DOI: 10.1200/jco.2022.40.16_suppl.3012.Peer-Reviewed Original ResearchDose-limiting toxicityExperienced dose-limiting toxicityCell lung cancerColorectal cancerPancreatic cancerLung cancerDose levelsSolid tumorsNon-small cell lung cancerCommon treatment-related gradeGrade 3 lung infectionStage IISmall cell lung cancerPhase I clinical trialDose-expansion cohortsGrade 3 diarrheaMutant solid tumorsPhase II doseTreatment-related gradeGrade 2 diarrheaAdvanced solid tumorsManageable side effectsDose-escalation designMutant colorectal cancerEfficacy of irinotecan
2021
Phase 1 Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844)
Roussos Torres ET, Rafie C, Wang C, Lim D, Brufsky A, LoRusso P, Eder JP, Chung V, Downs M, Geare M, Piekarz R, Streicher H, Anforth L, Rudek MA, Zhu Q, Besharati S, Cimino-Mathews A, Anders RA, Stearns V, Jaffee EM, Connolly RM. Phase 1 Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844). Clinical Cancer Research 2021, 27: clincanres.5017.2021. PMID: 34135021, PMCID: PMC8563383, DOI: 10.1158/1078-0432.ccr-20-5017.Peer-Reviewed Original ResearchConceptsCD8/FOXP3 ratioAdvanced solid tumorsAdverse eventsAddition of ICIFOXP3 ratioSolid tumorsGrade 3/4 adverse eventsRegulatory T cell ratioTreatment-related adverse eventsImmune checkpoint inhibitor efficacyTriple-negative breast cancerMulticenter phase I clinical trialPhase I clinical trialObjective response ratePhase II doseT cell ratioCheckpoint inhibitor efficacyPhase 1 studyCombination of entinostatHistone deacetylase inhibitor entinostatRECIST 1.1Primary endpointSecondary endpointsComplete responseDose escalation
2020
Clinical experience of ONC201 in patients with recurrent H3 K27M-mutant spinal cord glioma.
Kurz S, Tarapore R, Odia Y, Butowski N, Koschmann C, Aguilera D, MacDonald T, Lu G, Allen J, Oster W, Mehta M, Chi A, Wen P. Clinical experience of ONC201 in patients with recurrent H3 K27M-mutant spinal cord glioma. Journal Of Clinical Oncology 2020, 38: 2563-2563. DOI: 10.1200/jco.2020.38.15_suppl.2563.Peer-Reviewed Original ResearchSingle agent groupSpinal cord tumorsCombination groupCord tumorsPediatric patientsSpinal cordH3 K27M mutationMedian survival time rangesMedian follow-up timePhase I clinical trialPhase II clinical trialK27M mutationSurvival time rangesClinical experienceSpinal cord gliomasFollow-up timeHigh-grade gliomasII clinical trialsDose reductionDRD2 antagonistsMedian ageProlonged survivalAgent groupDiffuse gliomasUnfavorable prognosisPhase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma
Kaley TJ, Panageas KS, Pentsova EI, Mellinghoff IK, Nolan C, Gavrilovic I, DeAngelis LM, Abrey LE, Holland EC, Omuro A, Lacouture ME, Ludwig E, Lassman AB. Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma. Annals Of Clinical And Translational Neurology 2020, 7: 429-436. PMID: 32293798, PMCID: PMC7187704, DOI: 10.1002/acn3.51009.Peer-Reviewed Original ResearchConceptsRecurrent malignant gliomaDose-limiting toxicityMTOR inhibitor temsirolimusMalignant gliomasAkt inhibitor perifosinePhase I clinical trialDose level 3Dose level 7Phase II doseSynergistic anti-tumor effectKarnofsky performance statusPhase I trialDeadly primary brain cancerPI3K/Akt/mTOR axisPrimary brain cancerAkt/mTOR axisAnti-tumor effectsPotential therapeutic targetMost malignant gliomasPrior therapyTemsirolimus dosePerformance statusI trialIntracerebral hemorrhageCombined therapyAdenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer
Fong L, Hotson A, Powderly JD, Sznol M, Heist RS, Choueiri TK, George S, Hughes BGM, Hellmann MD, Shepard DR, Rini BI, Kummar S, Weise AM, Riese MJ, Markman B, Emens LA, Mahadevan D, Luke JJ, Laport G, Brody JD, Hernandez-Aya L, Bonomi P, Goldman JW, Berim L, Renouf DJ, Goodwin RA, Munneke B, Ho PY, Hsieh J, McCaffery I, Kwei L, Willingham SB, Miller RA. Adenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer. Cancer Discovery 2020, 10: 40-53. PMID: 31732494, PMCID: PMC6954326, DOI: 10.1158/2159-8290.cd-19-0980.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Renal CellDrug Resistance, NeoplasmFemaleFollow-Up StudiesFuransHumansKidney NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisPyridinesPyrimidinesReceptor, Adenosine A2ASalvage TherapySurvival RateConceptsRenal cell cancerPretreatment tumor biopsiesClinical responseGene expression signaturesCell cancerTumor biopsiesPD-1/PD-L1 inhibitorsPD-1/PD-L1Refractory renal cell cancerPhase I clinical trialL1 combination therapyRecruitment of CD8Targetable immune checkpointsDurable clinical benefitPD-L1 inhibitorsT cell repertoireAdenosine 2A receptorAntitumor immunityReceptor blockadeImmune checkpointsPD-L1L1 antibodyClinical benefitCombination therapyImmune cells
2019
Evaluation of Electronic Activity Monitors (EAMs) during phase I clinical trials.
Scaranti M, Sundar R, Daly R, Collins D, Dolling D, Gennatas S, Rao Baikady B, Kaye S, Banerji U, Lopez J, De Bono J, Minchom A. Evaluation of Electronic Activity Monitors (EAMs) during phase I clinical trials. Journal Of Clinical Oncology 2019, 37: e18175-e18175. DOI: 10.1200/jco.2019.37.15_suppl.e18175.Peer-Reviewed Original ResearchPhase I trialI trialMean step countPhase I clinical trialPatient's physical functionHeart ratePredicting Patient SurvivalDrug Development UnitStep countsECOG PSPhysical functionPatient survivalElectronic activity monitorsMedical oncologistsRecord heart ratePatient groupPhysician biasTreatment cyclesTreatment decisionsPatientsActivity monitoringPatient outcomesStatistical significanceOSPhysiciansUnlocking PARP inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform.
Bindra R, Sundaram R, Aiello R, Marshall D, Bourassa P, Csengery J, Zhang Q, Robinson B, lopresti-Morrow L, Bechtold J, Tylaska L, Paradis T, Paralkar V, Hellsund P, Glazer P. Unlocking PARP inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform. Journal Of Clinical Oncology 2019, 37: e14664-e14664. DOI: 10.1200/jco.2019.37.15_suppl.e14664.Peer-Reviewed Original ResearchHomologous recombination deficiencyHRD statusAnti-cancer agentsClinical trialsSignificant bone marrow toxicityTumor cellsInhibitor efficacyPhase I clinical trialIND-enabling studiesDose-limiting toxicityBone marrow toxicitySignificant tumor cell killingSmall molecule anti-cancer agentNormal tissue toxicityTumor cell killingTumor-targeting approachesPARP inhibitor efficacyRelevant chemotherapyVivo tumor modelsMarrow toxicityBRCA1/2 mutationsComplete sparingBone marrowSolid tumorsChemotherapyProspective phase I multi-institutional trial of PD-1 blockade with pembrolizumab during concurrent chemoradiation for locally advanced, unresectable non-small cell lung cancer.
Jabbour S, Berman A, Decker R, Lin Y, Feigenberg S, Gettinger S, Aggarwal C, Langer C, Simone C, Bradley J, Aisner J, Malhotra J. Prospective phase I multi-institutional trial of PD-1 blockade with pembrolizumab during concurrent chemoradiation for locally advanced, unresectable non-small cell lung cancer. Journal Of Clinical Oncology 2019, 37: 8511-8511. DOI: 10.1200/jco.2019.37.15_suppl.8511.Peer-Reviewed Original ResearchImmune-related adverse eventsStage III NSCLCDose limiting toxicitiesChemoradiation therapyPD-1iDay 29Unresectable non-small cell lung cancerDay 1Prospective phase I clinical trialNon-small cell lung cancerDeath ligand 1 (PD-L1) inhibitionPhase I clinical trialDefinitive chemoradiation therapyGrade 3 hyperglycemiaPD-1 blockadeFurther prospective studiesCell lung cancerMulti-institutional trialDose cohortsMedian PFSQ3 weeksConcurrent chemoradiationDefinitive RTAdverse eventsInterstitial nephritis
2018
A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials
Garces A, Ang J, Ameratunga M, Chénard-Poirier M, Dolling D, Diamantis N, Seeramreddi S, Sundar R, de Bono J, Lopez J, Banerji U. A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials. European Journal Of Cancer 2018, 104: 32-38. PMID: 30316017, PMCID: PMC6259582, DOI: 10.1016/j.ejca.2018.08.019.Peer-Reviewed Original ResearchConceptsPhase I clinical trialElectrolyte abnormalitiesBaseline hypoalbuminaemiaOverall survivalClinical significanceDose-limiting toxicity windowPrognostic factors of OSOncology phase I trialsInferior median OSFactors of OSPhase I patientsPhase I trialRetrospective chart reviewSerum albumin levelAssociated with hypomagnesaemiaRoyal Marsden HospitalCox regression analysisPhase I populationDrug Development UnitMedian OSPrognostic factorsPrognostic significanceI patientsI trialAlbumin levelsClinical outcomes of adolescents and young adults with advanced solid tumours participating in phase I trials
Sundar R, McVeigh T, Dolling D, Petruckevitch A, Diamantis N, Ang J, Chenard-Poiriér M, Collins D, Lim J, Ameratunga M, Khan K, Kaye S, Banerji U, Lopez J, George A, de Bono J, van der Graaf W. Clinical outcomes of adolescents and young adults with advanced solid tumours participating in phase I trials. European Journal Of Cancer 2018, 101: 55-61. PMID: 30025230, DOI: 10.1016/j.ejca.2018.06.003.Peer-Reviewed Original ResearchConceptsPhase I trialPhase I clinical trialAdvanced solid tumorsI trialOverall survivalAYA patientsSolid tumorsCancer syndromesCohort of AYA patientsMolecular characterisation of tumoursOutcomes of AYA patientsClinical benefit rateMedian overall survivalOutcomes of AYAsSomatic genetic aberrationsSignificant family historyRoyal Marsden HospitalHereditary cancer syndromesCharacterisation of tumoursTherapeutic treatment optionsClinical outcomes of adolescentsClinical trial dataDrug Development UnitYoung adultsGenetic aberrationsThe role of genomic profiling in adolescents and young adults (AYAs) with advanced cancer participating in phase I clinical trials
McVeigh T, Sundar R, Diamantis N, Kaye S, Banerji U, Lopez J, de Bono J, van der Graaf W, George A. The role of genomic profiling in adolescents and young adults (AYAs) with advanced cancer participating in phase I clinical trials. European Journal Of Cancer 2018, 95: 20-29. PMID: 29614442, PMCID: PMC6296443, DOI: 10.1016/j.ejca.2018.02.028.Peer-Reviewed Original ResearchConceptsDrug Development UnitGermline testingAdvanced cancerPhase I clinical trialTumor testingPersonal history of cancerAdvanced solid tumorsProportion of AYAsRoyal Marsden HospitalHistory of cancerAt-risk relativesCommon cancer typesYoung adultsDepartmental databaseClinicopathological featuresSolid tumorsChart reviewFamily risk factorsGermline mutationsPathogenic variantsStudy cohortCancer predispositionGenomic profilingPatient managementGenetic testing
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