2024
Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations
Yasin F, Sokol E, Vasan N, Pavlick D, Huang R, Pelletier M, Levy M, Pusztai L, Lacy J, Zhang J, Ross J, Cecchini M. Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations. The Oncologist 2024, oyae259. PMID: 39401325, DOI: 10.1093/oncolo/oyae259.Peer-Reviewed Original ResearchAdvanced colorectal cancerPIK3CA mutationsColorectal cancerPI3K inhibitionPI3K inhibitorsBurden of colorectal cancerActivating mutationsResponse to PI3K inhibitionSensitive to PI3K inhibition.Foundation Medicine databaseMetastatic colorectal cancerClinically relevant mutationsMicrosatellite instability-highPI3K signalingTumor DNAPIK3CA variantsClinical carePIK3CA oncogeneClinical variablesE545KGenomic profilingPIK3CAE542KMedicine DatabasePatientsDeep-Transfer-Learning–Based Natural Language Processing of Serial Free-Text Computed Tomography Reports for Predicting Survival of Patients With Pancreatic Cancer
Kim S, Kim S, Kim E, Cecchini M, Park M, Choi J, Kim S, Hwang H, Kang C, Choi H, Shin S, Kang J, Lee C. Deep-Transfer-Learning–Based Natural Language Processing of Serial Free-Text Computed Tomography Reports for Predicting Survival of Patients With Pancreatic Cancer. JCO Clinical Cancer Informatics 2024, 8: e2400021. PMID: 39151114, DOI: 10.1200/cci.24.00021.Peer-Reviewed Original ResearchConceptsArea under the receiver operating characteristic curveSurvival of patientsCT reportsPancreatic cancerNatural language processingC-indexPredicting survivalOverall survival of patientsTertiary hospitalPredicting 1-year survivalPredicting survival of patientsImproved C-indexSurvival informationPancreatic cancer survivalReceiver operating characteristic curveInternal test data setNLP modelsComputed tomography reportsLanguage processingKorean tertiary hospitalOverall survivalConsecutive patientsActual survivalConcordance indexPatientsPerioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer
Cecchini M, Salem R, Robert M, Czerniak S, Blaha O, Zelterman D, Rajaei M, Townsend J, Cai G, Chowdhury S, Yugawa D, Tseng R, Arbelaez C, Jiao J, Shroyer K, Thumar J, Kortmansky J, Zaheer W, Fischbach N, Persico J, Stein S, Khan S, Cha C, Billingsley K, Kunstman J, Johung K, Wiess C, Muzumdar M, Spickard E, Aushev V, Laliotis G, Jurdi A, Liu M, Escobar-Hoyos L, Lacy J. Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer. JAMA Oncology 2024, 10: 1027-1035. PMID: 38900452, PMCID: PMC11190830, DOI: 10.1001/jamaoncol.2024.1575.Peer-Reviewed Original ResearchProgression-free survivalPancreatic ductal adenocarcinomaOverall survivalCtDNA levelsPhase 2 nonrandomized controlled trialAnalysis of circulating tumor DNAMedian progression-free survivalResectable pancreatic ductal adenocarcinomaControlled trialsAssess surgical candidacyBaseline ctDNA levelModified 5-fluorouracilResectable pancreatic cancerPancreatic protocol computed tomographyAssociated with recurrenceTumor molecular featuresAggressive malignant tumorKaplan-Meier estimatesRandomized clinical trialsStandard of careCtDNA-positivePreoperative cyclesNonrandomized controlled trialsUnresectable diseaseModified FOLFIRINOXAssociation of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma
Botta G, Abdelrahim M, Drengler R, Aushev V, Esmail A, Laliotis G, Brewer C, George G, Abbate S, Chandana S, Tejani M, Malla M, Bansal D, Rivero-Hinojosa S, Spickard E, McCormick N, Cecchini M, Lacy J, Fei N, Kasi P, Kasi A, Dayyani F, Hanna D, Sharma S, Malhotra M, Aleshin A, Liu M, Jurdi A. Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma. The Oncologist 2024, 29: 859-869. PMID: 39022993, PMCID: PMC11449101, DOI: 10.1093/oncolo/oyae155.Peer-Reviewed Original ResearchMolecular residual diseasePancreatic ductal adenocarcinomaPatient survival outcomesCtDNA detectionSurvival outcomesStage I–III pancreatic ductal adenocarcinomaAssociated with shorter DFSMedian follow-up timeFollow-up timeCtDNA levelsResidual diseaseShorter DFSPrognostic factorsPancreatic adenocarcinomaAssociated with patient survival outcomesDuctal adenocarcinomaRetrospective analysisDiagnosed patientsMultivariate analysisSurveillance periodPatientsPlasma samplesTumor informationWhole exomeSurveillance windowProofreading the way: immune checkpoint inhibitors in polymerase ε/polymerase δ (POLE/POLD1)-altered colorectal cancer
Cecchini M, Sundar R. Proofreading the way: immune checkpoint inhibitors in polymerase ε/polymerase δ (POLE/POLD1)-altered colorectal cancer. Annals Of Oncology 2024, 35: 582-584. PMID: 38910015, DOI: 10.1016/j.annonc.2024.04.006.Commentaries, Editorials and LettersInterim results of the randomized phase 2 cohort of study FW-2020-01 assessing the efficacy, safety and pharmacodynamics of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer.
Macarulla T, Cecchini M, Garcia-Carbonero R, Golan T, Perets R, Borazanci E, Pedregal M, Ponz-Sarvise M, Al Hallak M, Pant S, Boni V, Saavedra O, de Miguel M, Leal A, Muñoz Martín A, Sauri T, Schickler M. Interim results of the randomized phase 2 cohort of study FW-2020-01 assessing the efficacy, safety and pharmacodynamics of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer. Journal Of Clinical Oncology 2024, 42: lba4143-lba4143. DOI: 10.1200/jco.2024.42.17_suppl.lba4143.Peer-Reviewed Original ResearchDisease control rateProgression free survivalPancreatic ductal adenocarcinomaCarcinoembryonic antigen cell adhesion molecule 1Nal-IRIGemcitabine/nab-paclitaxelOverall survivalData cut-off dateRandomized phase 2 studyMedian follow-up timeCut-off dateAdequate organ functionAdvanced/metastatic pancreatic cancerPhase 2 studyLog-rank testFollow-up timeCell adhesion molecule 1Adhesion molecule 1Liposomal irinotecanFree survivalLine therapyOpen-labelSystemic therapyPFS-HRPrimary endpointA single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer
Verma N, Johung K, Kortmansky J, Zaheer W, Lacy J, Cecchini M, Stein S, Cheng Y, Lam W, Liu S, Reddy V, Hochster H, Higgins S. A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer. Journal Of Gastrointestinal Oncology 2024, 15: 1050-1059. PMID: 38989411, PMCID: PMC11231844, DOI: 10.21037/jgo-24-23.Peer-Reviewed Original ResearchA phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation.
Heumann T, Stockton S, Cecchini M, Aljumaily R, Shyr C, Whisenant J, Starr J, Dayyani F, Baranda J, Trikalinos N, Ivy S, LoRusso P, Das S, Gore S, Beumer J, Berlin J. A phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation. Journal Of Clinical Oncology 2024, 42: 3077-3077. DOI: 10.1200/jco.2024.42.16_suppl.3077.Peer-Reviewed Original ResearchAdvanced solid tumorsMaximum tolerated doseDose escalationSolid tumorsPhase I study of irinotecanRecommended phase 2 doseRefractory advanced solid tumorsPhase 2 dosePhase I studyAnti-tumor activityBiweekly irinotecanInhibitor irinotecanIrinotecan exposureWeekly irinotecanTolerated doseDosing scheduleCancer xenograftsAdult patientsIrinotecanAssess safetyATR inhibitorsElimusertibSecondary objectivesDoseStandard careA phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation.
Stockton S, Shyr C, Cecchini M, Aljumaily R, Halfdanarson T, Sonbol M, Whisenant J, Ivy S, LoRusso P, Das S, Gore S, Berlin J, Beumer J, Heumann T. A phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation. Journal Of Clinical Oncology 2024, 42: 3076-3076. DOI: 10.1200/jco.2024.42.16_suppl.3076.Peer-Reviewed Original ResearchMaximum tolerated doseDose escalationDose levelsMedian progression-free survivalRecommended phase 2 doseRefractory advanced solid tumorsResults of dose escalationTreatment-related adverse eventsSmall cell lung cancerDisease control ratePhase 2 dosePhase Ia studyDose-limiting toxicityProgression-free survivalAdvanced solid tumorsPhase I studyCell lung cancerAnti-tumor activityExpansion cohortPartial responseTolerated doseTopotecan exposureStudy drugCancer xenograftsRespiratory failurePersonalized risk assessment of new onset depression in long-term cancer survivors.
Taylor M, Westvold S, Long J, Hyslop T, Wang S, Cecchini M, Leapman M, Leeds I, Lustberg M, Spees L, Wheeler S, Gross C, Oeffinger K, Dinan M. Personalized risk assessment of new onset depression in long-term cancer survivors. Journal Of Clinical Oncology 2024, 42: e13798-e13798. DOI: 10.1200/jco.2024.42.16_suppl.e13798.Peer-Reviewed Original ResearchHistory of depressionIncidence of depressionCumulative incidence of depressionRisk of developing depressionLong-term survivorsPredictors of depressionCancer survivorsDisease specific factorsCumulative incidenceNon-HispanicHigher risk of developing depressionRectal cancerLong-term cancer survivorsBreast cancer survivorsCensus tract povertyColon cancerEpisodes of bipolar I disorderPrevalence of depressionMean survival time modelsDiagnosis of depressionReceipt of treatmentAssociated with prior historyHormone receptor statusPatients aged <Adjuvant endocrine therapyARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC).
Wainberg Z, Han S, Lee S, Lee K, Kopetz S, Mizrahi J, Hong Y, Ghiringhelli F, Italiano A, Tougeron D, Beagle B, Boakye M, Zhao T, Rhee J, Nuyten D, Cecchini M. ARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC). Journal Of Clinical Oncology 2024, 42: 3508-3508. DOI: 10.1200/jco.2024.42.16_suppl.3508.Peer-Reviewed Original ResearchProgression-free survivalMetastatic colorectal cancerOverall survivalCohort BActivation of effector T cellsManagement of metastatic colorectal cancerAnti-PD-1 antibodyTreat metastatic colorectal cancerTreated with 5-FURandomized phase II clinical trialIrinotecan-containing regimensPhase Ib/II trialPhase II clinical trialEffector T cellsAdenosine receptor blockadeCohort of patientsII clinical trialsIrinotecan regimensMFOLFOX-6OS improvementReceptor blockadePrimary endpointProspective trialsReceptor antagonistSecondary endpointsA first-in-human, phase 1/2 trial of FOG-001, a β-catenin:TCF antagonist, in patients with locally advanced or metastatic solid tumors.
Papadopoulos K, Rodon Ahnert J, Khushman M, Sharma S, Pelster M, Cecchini M, Kummar S, Choi M, Akella L, Garofalo A, Yu Z, Iyer V, Nguyen M, Orford K, Klempner S. A first-in-human, phase 1/2 trial of FOG-001, a β-catenin:TCF antagonist, in patients with locally advanced or metastatic solid tumors. Journal Of Clinical Oncology 2024, 42: tps3175-tps3175. DOI: 10.1200/jco.2024.42.16_suppl.tps3175.Peer-Reviewed Original ResearchNon-small cell lung cancerMSS colorectal cancerMetastatic solid tumorsSolid tumorsColorectal cancerAdenomatous polyposis coliT cell factorB-cateninAntitumor activityWnt/b-cateninPhase 1/2 trialCell lung cancerFirst-in-humanTumor growth inhibitionActivate oncogenic pathwaysIntravenous (IVWnt pathwayPathway activating mutationsWnt/b-catenin pathwayWnt pathway genesCurative chemoradiationDose escalationDose expansionGastric/GEJ cancerEscalating dosesAuthor Correction: Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting
Prosz A, Sahgal P, Huffman B, Sztupinszki Z, Morris C, Chen D, Börcsök J, Diossy M, Tisza V, Spisak S, Likasitwatanakul P, Rusz O, Csabai I, Cecchini M, Baca Y, Elliott A, Enzinger P, Singh H, Ubellaker J, Lazaro J, Cleary J, Szallasi Z, Sethi N. Author Correction: Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting. Npj Precision Oncology 2024, 8: 98. PMID: 38710943, PMCID: PMC11074298, DOI: 10.1038/s41698-024-00587-w.Peer-Reviewed Original ResearchMutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting
Prosz A, Sahgal P, Huffman B, Sztupinszki Z, Morris C, Chen D, Börcsök J, Diossy M, Tisza V, Spisak S, Likasitwatanakul P, Rusz O, Csabai I, Cecchini M, Baca Y, Elliott A, Enzinger P, Singh H, Ubellaker J, Lazaro J, Cleary J, Szallasi Z, Sethi N. Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting. Npj Precision Oncology 2024, 8: 87. PMID: 38589664, PMCID: PMC11001913, DOI: 10.1038/s41698-024-00561-6.Peer-Reviewed Original ResearchNucleotide excision repairGastric cancer cell linesNucleotide excision repair-deficientPlatinum chemotherapyHR deficiencyCancer cell linesPARP inhibitorsHomologous recombinationGenome sequence dataSensitivity to platinum chemotherapySingle-cell RNA sequencingCell linesHR-deficient cancersDNA repair pathwaysSensitivity to cisplatinRad51 foci assaysMutational signature analysisSequence dataGenomic featuresWhole exomeInduce apoptosisRNA sequencingGastroesophageal adenocarcinomaRepair pathwaysHRD scoreThe Perioperative Modified FOLFIRINOX Clinical Trial for Resectable Pancreatic Cancer
Michael Cecchini MD, Ronald R. Salem MD, Marie Robert MD, Suzanne Czerniak MD PhD, Ondrej Blaha Phd, Daniel Zelterman PhD, Moein Rajaei PhD, Jeffrey P. Townsend PhD, Guoping Cai MD MS, Sumedha Chowdhury, Deanne Yugawa BS, Robert Tseng BS, Carlos Mejia Arbelaez MD, Jingjing Jiao MD, Kenneth Shroyer MD PhD, Jaykumar Thumar MBBS, Jeremy Kortmansky MD, Wajih Zaheer MD, Neal Fischbach MD, Justin Persico MD, Stacey Stein MD, Sajid A. Khan MD, Charles Cha MD, Kevin G. Billingsley MD MBA, John W. Kunstman MD MHS, Kimberly L. Johung MD MHS, Christina Wiess BA, Mandar D. Muzumdar MD PhD, Erik Spickard PhD, Vasily N. Aushev PhD, George Laliotis MD MHA MPH MBA, Adham Jurdi MD, Minetta C. Liu MD, Luisa Escobar-Hoyos MsC PhD, Jill Lacy MD. The Perioperative Modified FOLFIRINOX Clinical Trial for Resectable Pancreatic Cancer. JAMA Oncology [Accepted 2/2/2024 ].Peer-Reviewed Original ResearchAbstract B117: Phase 1 study of CM24 in combination with nivolumab in patients with advanced pancreatic cancer - Survival, potential biomarker and effect on neutrophil extracellular traps (NETs)
Borazanci E, Pant S, Perets R, Golan T, Al Hallak M, Cecchini M, Maierson T, David H, Schickler M, Reuveni H. Abstract B117: Phase 1 study of CM24 in combination with nivolumab in patients with advanced pancreatic cancer - Survival, potential biomarker and effect on neutrophil extracellular traps (NETs). Cancer Research 2024, 84: b117-b117. DOI: 10.1158/1538-7445.panca2023-b117.Peer-Reviewed Original ResearchPancreatic ductal adenocarcinoma patientsTumor-infiltrating lymphocytesPancreatic ductal adenocarcinomaNeutrophil extracellular trapsCarcinoembryonic antigen cell adhesion molecule 1Dose-escalation partPancreatic cancer survivalImmune evasionExtracellular trapsEscalation partPatient biopsiesPotential biomarkersRandomized phase 2 studyCompared to healthy volunteersControl immune evasionDisease control ratePhase 1/2 studyAnti-tumor immunitySecond-line therapyCancer survivalPhase 2 studyPhase 1 studyCell adhesion molecule 1Adhesion molecule 1Patient survival dataAbstract 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
NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma
Cecchini M, Cleary J, Shyr Y, Chao J, Uboha N, Cho M, Shields A, Pant S, Goff L, Spencer K, Kim E, Stein S, Kortmansky J, Canosa S, Sklar J, Swisher E, Radke M, Ivy P, Boerner S, Durecki D, Hsu C, LoRusso P, Lacy J. NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma. British Journal Of Cancer 2023, 130: 476-482. PMID: 38135713, PMCID: PMC10844282, DOI: 10.1038/s41416-023-02534-1.Peer-Reviewed Original ResearchAbstract A123: Circulating tumor DNA (ctDNA) genomic and epigenomic profiling (GuardantINFINITY) for diagnosis of DNA damage repair (DDR) loss of function (LOF) and response monitoring in the TRESR and ATTACC trials
Rosen E, Schonhoft J, Silverman I, Yablonovitch A, Sethuraman S, Nejad P, Ulanet D, Yang J, Kim I, Fei K, Xu Y, Lagow E, Zhang S, Cai M, Koehler M, Carneiro B, Lheureux S, Cecchini M, Herzberg B, Reis-Filho J, Rimkunas V, Yap T. Abstract A123: Circulating tumor DNA (ctDNA) genomic and epigenomic profiling (GuardantINFINITY) for diagnosis of DNA damage repair (DDR) loss of function (LOF) and response monitoring in the TRESR and ATTACC trials. Molecular Cancer Therapeutics 2023, 22: a123-a123. DOI: 10.1158/1535-7163.targ-23-a123.Peer-Reviewed Original ResearchCirculating tumor DNAVariant allele frequencyDNA damage repairEpigenomic profilingTumor DNADamage repairResponse monitoringCirculating tumor DNA sequencingLow variant allele frequencyTreated with PARPiPhase 1 studyCell-free DNAMolecular responseIntragenic deletionsEpigenetic analysisAllele frequenciesRad3-relatedCH variantsGenomic alterationsOn-treatmentClinical outcomesPancreatic cancerAtaxia telangiectasiaPathogenic alterationsEvaluable ptsAbstract A137: Pharmacokinetics and pharmacodynamics of IGM-8444, a first-in-class engineered pentameric DR5-targeting agonist IgM monoclonal antibody, in patients with R/R and newly diagnosed cancers
Hernandez G, Bilic S, Guan Y, So J, Bhattacharya S, Wang B, Kotturi M, Oyasu M, Desbois M, Cao Y, Humke E, Ahern S, Sinclair A, Ulahannan S, Subbiah V, Pelster M, Lorusso P, Falchook G, Wang J, Barve M, Grewal J, Chow W, Henry J, Cecchini M, Takimoto C, Leabman M. Abstract A137: Pharmacokinetics and pharmacodynamics of IGM-8444, a first-in-class engineered pentameric DR5-targeting agonist IgM monoclonal antibody, in patients with R/R and newly diagnosed cancers. Molecular Cancer Therapeutics 2023, 22: a137-a137. DOI: 10.1158/1535-7163.targ-23-a137.Peer-Reviewed Original ResearchCleaved caspase-3Single agentNewly diagnosed cancerIgM monoclonal antibodyPreclinical mouse tumor modelsIgM antibodiesCasp-3Monoclonal antibodiesInduce tumor cell apoptosisPopulation PK modelPopulation PK analysisDose-dependent increaseMouse tumor modelsTumor cell apoptosisTerminal half-lifeTreatment-related increasesDose-dependent efficacyCleaved caspase-3 levelsEffects of ADAADA titersTwo-compartment modelPharmacodynamic changesTargeted therapyEfficacious dosePK analysis