2024
Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study.
Philip P, Sahai V, Bahary N, Mahipal A, Kasi A, Rocha Lima C, Alistar A, Oberstein P, Golan T, Metges J, Lacy J, Fountzilas C, Lopez C, Ducreux M, Hammel P, Salem M, Bajor D, Benson A, Luther S, Pardee T, Van Cutsem E. Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study. Journal Of Clinical Oncology 2024, jco2302659. PMID: 39088774, DOI: 10.1200/jco.23.02659.Peer-Reviewed Original ResearchMetastatic pancreatic adenocarcinomaOverall survivalCPI-613Randomized phase III trialTreatment-emergent adverse eventsExperimental armDifficult-to-treat diseaseFavorable performance statusProgression-free survivalTreatment naive patientsFirst-line therapyPhase I studyPhase III trialsMedian OSMetastatic adenocarcinomaIII trialsFirst-linePerformance statusPancreatic adenocarcinomaAdverse eventsDevimistatDay 1Disease progressionControl armPatientsA 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 ResearchCombining antivascular endothelial growth factor and anti-epidermal growth factor receptor antibodies: randomized phase II study of irinotecan and cetuximab with/without ramucirumab in second-line colorectal cancer (ECOG-ACRIN E7208)
Hochster H, Catalano P, Weitz M, Mitchell E, Cohen D, O’Dwyer P, Faller B, Kortmansky J, O’Hara M, Kricher S, Lacy J, Lenz H, Verma U, Benson A. Combining antivascular endothelial growth factor and anti-epidermal growth factor receptor antibodies: randomized phase II study of irinotecan and cetuximab with/without ramucirumab in second-line colorectal cancer (ECOG-ACRIN E7208). Journal Of The National Cancer Institute 2024, djae114. PMID: 38775718, DOI: 10.1093/jnci/djae114.Peer-Reviewed Original ResearchProgression-free survivalDisease-control ratePhase 3 trialColorectal cancerAnti-VEGFAnti-VEGFRAnti-EGFRKRAS-wild type colorectal cancerPhase II study of irinotecanKRAS wild-type colorectal cancerMedian progression-free survivalRandomized phase II studyKRAS wild-type tumorsWild-type colorectal cancerAnti-VEGFR antibodiesAnti-VEGF drugsTreated with ICSecond-line treatmentStudy of irinotecanWild-type tumorsAdvanced colorectal cancerPhase 2 studyAnti-EGFR antibodiesAnti-VEGF antibodyECOG PS
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 ResearchQuantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Cecchini M, Zhang J, Wei W, Sklar J, Lacy J, Zhong M, Kong Y, Zhao H, DiPalermo J, Devine L, Stein S, Kortmansky J, Johung K, Bindra R, LoRusso P, Schalper K. Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer. Cancer Research Communications 2023, 3: 1132-1139. PMID: 37387791, PMCID: PMC10305782, DOI: 10.1158/2767-9764.crc-23-0045.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMGMT protein expressionColorectal cancerStable diseaseQuantitative immunofluorescenceT cellsProtein expressionPromoter hypermethylationLow MGMT protein expressionPARP inhibitorsRadiographic tumor regressionMetastatic colorectal cancerAdvanced colorectal cancerPretreatment tumor biopsiesEffector T cellsTumor-infiltrating lymphocytesMGMT proteinDNA repair biomarkersBaseline CD8Eligible patientsIncreased CD8Methylguanine-DNA methyltransferaseObjective responseProgressive diseaseImmune markersPre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer
Peters G, Talcott W, Peters N, Dhanasopan A, Lacy J, Cecchini M, Kortmansky J, Stein S, Lattanzi S, Park H, Boffa D, Johung K, Jethwa K. Pre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer. Journal Of Gastrointestinal Oncology 2023, 14: 1181-1192. PMID: 37435226, PMCID: PMC10331751, DOI: 10.21037/jgo-22-1005.Peer-Reviewed Original ResearchProgression-free survivalMedian progression-free survivalOverall survivalIC-CRTInduction chemotherapySingle-institution retrospective cohort studyPre-operative chemoradiotherapyAdvanced esophageal cancerAdvanced esophageal carcinomaPathologic complete responseRetrospective cohort studyKaplan-Meier methodSubset of patientsProportional hazards regressionCycles of inductionAdenocarcinoma histologyCRT cohortCohort studyComplete responsePathologic responseTreatment cohortsDistant metastasisHazards regressionEsophageal cancerEsophageal carcinomaEsophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.
Ajani J, D'Amico T, Bentrem D, Cooke D, Corvera C, Das P, Enzinger P, Enzler T, Farjah F, Gerdes H, Gibson M, Grierson P, Hofstetter W, Ilson D, Jalal S, Keswani R, Kim S, Kleinberg L, Klempner S, Lacy J, Licciardi F, Ly Q, Matkowskyj K, McNamara M, Miller A, Mukherjee S, Mulcahy M, Outlaw D, Perry K, Pimiento J, Poultsides G, Reznik S, Roses R, Strong V, Su S, Wang H, Wiesner G, Willett C, Yakoub D, Yoon H, McMillian N, Pluchino L. Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology. Journal Of The National Comprehensive Cancer Network 2023, 21: 393-422. PMID: 37015332, DOI: 10.6004/jnccn.2023.0019.Peer-Reviewed Original ResearchConceptsEsophagogastric junction cancerSquamous cell carcinomaJunction cancerMetastatic diseaseSystemic therapyNCCN Clinical Practice GuidelinesEsophageal squamous cell carcinomaMajor global health problemBest supportive careManagement of recurrentMultidisciplinary team managementClinical practice guidelinesTreatment of patientsGlobal health problemMicrosatellite instability statusNCCN guidelinesPalliative managementSupportive careEsophagogastric junctionCell carcinomaLower esophagusEsophageal cancerHER2 statusTumor locationBiomarker testingAtezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform
Ko A, Kim K, Siveke J, Lopez C, Lacy J, O'Reilly E, Macarulla T, Manji G, Lee J, Ajani J, Alsina Maqueda M, Rha S, Lau J, Al-Sakaff N, Allen S, Lu D, Shemesh C, Gan X, Cha E, Oh D. Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform. The Oncologist 2023, 28: 553-e472. PMID: 36940261, PMCID: PMC10243783, DOI: 10.1093/oncolo/oyad022.Peer-Reviewed Original ResearchConceptsObjective response ratePancreatic ductal adenocarcinomaGrade 3/4 adverse eventsGrade 5 adverse eventsAdverse eventsGastric cancerDuctal adenocarcinomaPhase Ib/II trialAdvanced pancreatic ductal adenocarcinomaLimited clinical activitySafety of atezolizumabRecombinant human hyaluronidaseEligible patientsVersus ChemotherapyII trialPrimary endpointRECIST 1.1Early efficacySafety profileAtezolizumabClinical activitySafety signalsPEGPH20Response rateHuman hyaluronidaseEffect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma
Huffman B, Mallick A, Horick N, Wang-Gillam A, Hosein P, Morse M, Beg M, Murphy J, Mavroukakis S, Zaki A, Schlechter B, Sanoff H, Manz C, Wolpin B, Arlen P, Lacy J, Cleary J. Effect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma. JAMA Network Open 2023, 6: e2249720. PMID: 36602796, PMCID: PMC9856813, DOI: 10.1001/jamanetworkopen.2022.49720.Peer-Reviewed Original ResearchConceptsAdvanced pancreatic ductal adenocarcinomaPancreatic ductal adenocarcinomaObjective response rateProgression-free survivalSecond-line treatmentNab-paclitaxelOverall survivalClinical trialsDuctal adenocarcinomaRandomized phase II clinical trialMedian progression-free survivalGemcitabine/nab-paclitaxelCox proportional hazards analysisEnd pointPhase II clinical trialChemotherapy dose reductionsFirst-line FOLFIRINOXSecond-line gemcitabineMedian overall survivalPrimary end pointSecondary end pointsProportional hazards analysisSurvival of patientsLow performance statusPretreatment clinical variables
2022
Phase 3, multicenter, randomized study of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) as first-line therapy for patients with metastatic adenocarcinoma of the pancreas (AVENGER500).
Philip P, Bahary N, Mahipal A, Kasi A, Rocha Lima C, Alistar A, Oberstein P, Golan T, Sahai V, Metges J, Lacy J, Fountzilas C, Lopez C, Ducreux M, Hammel P, Salem M, Bajor D, Benson A, Buyse M, Van Cutsem E. Phase 3, multicenter, randomized study of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) as first-line therapy for patients with metastatic adenocarcinoma of the pancreas (AVENGER500). Journal Of Clinical Oncology 2022, 40: 4023-4023. DOI: 10.1200/jco.2022.40.16_suppl.4023.Peer-Reviewed Original ResearchProgression-free survivalMetastatic pancreatic cancerOverall response rateMedian overall survivalFirst-line therapyCPI-613Experimental armRandomized phase 3 trialStandard first-line therapyTreatment-emergent adverse eventsDoses of irinotecanTreatment-naïve patientsPhase 3 trialDuration of responseLimited treatment optionsPatient reported outcomesTest armIntolerable toxicityPrimary endpointSecondary endpointsAdverse eventsOverall survivalMetastatic adenocarcinomaTreatment optionsControl armAn Appraisal of Immunohistochemical Stain Use in Hepatic Metastasis Highlights the Effectiveness of the Individualized, Case-Based Approach: Analysis of Data From a Tertiary Care Medical Center.
Wang JD, Sebastian C, Walther Z, Suresh T, Lacy J, Zhang X, Jain D. An Appraisal of Immunohistochemical Stain Use in Hepatic Metastasis Highlights the Effectiveness of the Individualized, Case-Based Approach: Analysis of Data From a Tertiary Care Medical Center. Archives Of Pathology & Laboratory Medicine 2022, 147: 185-192. PMID: 35512224, DOI: 10.5858/arpa.2021-0457-oa.Peer-Reviewed Original ResearchConceptsLiver biopsyUnknown primaryIHC markersPrimary siteTrue carcinomaTertiary care medical centerAvailable clinicopathologic dataSquamous cell carcinomaClinicopathologic dataHepatic metastasesNonepithelial tumorsCell carcinomaInstitutional databaseClinical managementStain usePractice patternsNeuroendocrine neoplasmsImmunohistochemical markersMedical CenterMorphologic patternsIndividualized approachCarcinomaBiopsyMetastasisTumorsYale Precision Medicine Tumor Board: reawakening the guardian of the genome
Grant MJ, Finberg KE, Walther Z, Stein SM, Lacy J, Eder JP, Goldberg SB. Yale Precision Medicine Tumor Board: reawakening the guardian of the genome. The Lancet Oncology 2022, 23: 337-338. PMID: 35240081, DOI: 10.1016/s1470-2045(22)00037-7.Peer-Reviewed Case Reports and Technical NotesGastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.
Ajani JA, D'Amico TA, Bentrem DJ, Chao J, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Fanta P, Farjah F, Gerdes H, Gibson MK, Hochwald S, Hofstetter WL, Ilson DH, Keswani RN, Kim S, Kleinberg LR, Klempner SJ, Lacy J, Ly QP, Matkowskyj KA, McNamara M, Mulcahy MF, Outlaw D, Park H, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, Willett CG, Yakoub D, Yoon H, McMillian N, Pluchino LA. Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. Journal Of The National Comprehensive Cancer Network : JNCCN 2022, 20: 167-192. PMID: 35130500, DOI: 10.6004/jnccn.2022.0008.Peer-Reviewed Original Research
2021
Clinical outcomes of first line FOLFIRINOX vs . gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System
Patel T, Miccio J, Cecchini M, Srikumar T, Stein S, Kortmanksy J, Johung K, Lacy J. Clinical outcomes of first line FOLFIRINOX vs . gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System. Journal Of Gastrointestinal Oncology 2021, 0: 0-0. PMID: 35070386, PMCID: PMC8748034, DOI: 10.21037/jgo-21-202.Peer-Reviewed Original ResearchMetastatic pancreatic cancerFirst-line FOLFIRINOXTreatment discontinuationFFX groupDose modificationOverall survivalNab-paclitaxelPancreatic cancerGN groupComparative effectivenessMedian TTDFirst-line settingMedian overall survivalOutcomes of patientsTreatment-related toxicityFirst-line therapyKaplan-Meier methodRate of hospitalizationElectronic medical record systemAdjuvant gemcitabineChemotherapy toxicityDiscontinuation ratesLine therapyMedical record systemTreatment toxicity
2020
259 Phase Ib/II open-label, randomized evaluation of atezolizumab (atezo) + selicrelumab (seli) + gemcitabine+nab-paclitaxel (gem+nabP) or bevacizumab (bev) vs control in MORPHEUS-PDAC, -TNBC and -CRC
Manji G, Bahary N, Chung V, Dalenc F, Ducreux M, Gomez-Roca C, Im S, Kortmansky J, Lacy J, Segal N, Tredan O, Cirovic O, DuPree K, Lenain C, Lu D, Robert L, Xu J, Zhang X, Kim S. 259 Phase Ib/II open-label, randomized evaluation of atezolizumab (atezo) + selicrelumab (seli) + gemcitabine+nab-paclitaxel (gem+nabP) or bevacizumab (bev) vs control in MORPHEUS-PDAC, -TNBC and -CRC. 2020, a157-a158. DOI: 10.1136/jitc-2020-sitc2020.0259.Peer-Reviewed Original ResearchAssociation of Neoadjuvant Treatment Modality with Negative Margin and Pathologic Downstaging in Patients Undergoing Pancreatic Cancer Resection: A National Cancer Database Analysis
Miccio J, Mokhtech M, Jabbour S, Anker C, Patel T, Park H, Cecchini M, Salem R, Kuntsman J, Stein S, Kortmansky J, Lacy J, Narang A, Herman J, Haddock M, Hallemeier C, Johung K, Jethwa K. Association of Neoadjuvant Treatment Modality with Negative Margin and Pathologic Downstaging in Patients Undergoing Pancreatic Cancer Resection: A National Cancer Database Analysis. International Journal Of Radiation Oncology • Biology • Physics 2020, 108: e662. DOI: 10.1016/j.ijrobp.2020.07.1980.Peer-Reviewed Original ResearchThe Utility of Neoadjuvant Radiotherapy after Neoadjuvant Multiagent Chemotherapy in Patients with Localized Pancreatic Cancer
Miccio J, Talcott W, Patel T, Park H, Cecchini M, Salem R, Stein S, Kortmansky J, Lacy J, Johung K, Jethwa K. The Utility of Neoadjuvant Radiotherapy after Neoadjuvant Multiagent Chemotherapy in Patients with Localized Pancreatic Cancer. International Journal Of Radiation Oncology • Biology • Physics 2020, 108: e31-e32. DOI: 10.1016/j.ijrobp.2020.02.538.Peer-Reviewed Original ResearchMicrosatellite instability and KRAS mutation in stage 4 CRC: Prevalence, geographic discrepancies and outcomes from the National Cancer Database.
Uhlig J, Cecchini M, Stein S, Lacy J, Kim K. Microsatellite instability and KRAS mutation in stage 4 CRC: Prevalence, geographic discrepancies and outcomes from the National Cancer Database. Journal Of Clinical Oncology 2020, 38: e16052-e16052. DOI: 10.1200/jco.2020.38.15_suppl.e16052.Peer-Reviewed Original ResearchNational Cancer DatabaseOverall survivalKRAS statusKRAS mutationsMicrosatellite instabilityMicrosatellite statusCancer DatabaseCRC siteStage IV colorectal adenocarcinomaStage IV CRC patientsUnited States National Cancer DatabaseCox proportional hazards modelStage IV CRCKRAS mutation rateRight-sided CRCProportional hazards modelDistinct prognostic profilesStatistical interaction testsKRAS wildtypePatient demographicsCRC patientsMetastatic burdenCRC treatmentMultivariable analysisPrognostic profilePhase Ib/II open-label, randomized evaluation of 2L atezolizumab (atezo) + PEGPH20 versus control in MORPHEUS-pancreatic ductal adenocarcinoma (M-PDAC) and MORPHEUS-gastric cancer (M-GC).
Ko A, Lee J, ALSINA M, Ajani J, Bang Y, Chung H, Lacy J, Lopez C, Oh D, O'Reilly E, Siveke J, Allen S, Al-Sakaff N, Barak H, Lau J, Li S, Retiere A, Shemesh C, Zhang X, Kim K. Phase Ib/II open-label, randomized evaluation of 2L atezolizumab (atezo) + PEGPH20 versus control in MORPHEUS-pancreatic ductal adenocarcinoma (M-PDAC) and MORPHEUS-gastric cancer (M-GC). Journal Of Clinical Oncology 2020, 38: 4540-4540. DOI: 10.1200/jco.2020.38.15_suppl.4540.Peer-Reviewed Original ResearchSerious AEsPhase Ib/II trialPhase Ib/IIChemotherapy-free combinationsEarly efficacy signalsNew safety signalsDuration of responseSeparate randomized trialsRecombinant human hyaluronidaseGr 3Eligible ptsMedian PFSMetastatic PDACTumor hyaluronanCombination armMedian OSPrimary endpointII trialNab-paclitaxelPeripheral edemaEfficacy signalsExtracellular matrix modulatorsRandomized trialsPoor prognosisSafety profilePhase Ib/II open-label, randomized evaluation of 2L atezolizumab (atezo) + BL-8040 versus control in MORPHEUS-pancreatic ductal adenocarcinoma (M-PDAC) and MORPHEUS-gastric cancer (M-GC).
Oh D, Ajani J, Bang Y, Chung H, Lacy J, Lee J, Macarulla T, Manji G, O'Reilly E, Allen S, Al-Sakaff N, Barak H, Patel J, Pintoffl J, Shemesh C, Zhang W, Zhang X, Chau I. Phase Ib/II open-label, randomized evaluation of 2L atezolizumab (atezo) + BL-8040 versus control in MORPHEUS-pancreatic ductal adenocarcinoma (M-PDAC) and MORPHEUS-gastric cancer (M-GC). Journal Of Clinical Oncology 2020, 38: 712-712. DOI: 10.1200/jco.2020.38.4_suppl.712.Peer-Reviewed Original ResearchControl armPhase Ib/IIEarly efficacy signalsInjection-related reactionsImmune-mediated effectsSeparate randomized trialsHigh-affinity antagonistEvaluable ptsMetastatic PDACPrimary endpointRECIST 1.1II trialEfficacy signalsRandomized trialsSafety profileAtezoDuctal adenocarcinomaPK dataRandomized EvaluationCancerGr 3PDACTrialsWkEfficacy