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, 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, 42: 3692-3701. 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 armPatientsCombining 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, 116: 1487-1494. PMID: 38775718, PMCID: PMC11378308, 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
Pre-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 carcinomaEffect 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, 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 arm
2020
HALO 109-301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20) + nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA).
Tempero M, Van Cutsem E, Sigal D, Oh D, Fazio N, Macarulla T, Hitre E, Hammel P, Hendifar A, Bates S, Li C, De La Fouchardiere C, Heinemann V, Maraveyas A, Bahary N, Layos L, Sahai V, Zheng L, Lacy J, Bullock A. HALO 109-301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20) + nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA). Journal Of Clinical Oncology 2020, 38: 638-638. DOI: 10.1200/jco.2020.38.4_suppl.638.Peer-Reviewed Original ResearchMetastatic pancreatic ductal adenocarcinomaObjective response rateProgression-free survivalPhase 3 studyOverall survivalAdverse eventsTumor microenvironmentHazard ratioNab-paclitaxel/gemcitabineRandomized phase 2 studyMedian progression-free survivalIntolerable adverse eventsMedian overall survivalPhase 2 studyPancreatic ductal adenocarcinomaPegvorhyaluronidase alfaProphylactic enoxaparinRECIST v1.1Primary endpointSecondary endpointsTE eventsBaseline characteristicsMusculoskeletal eventsThromboembolism riskClinical outcomes
2019
1188PD Margetuximab (M) + pembrolizumab (P) for treatment of patients (pts) with HER2+ gastroesophageal adenocarcinoma (GEA) post-trastuzumab (T): Survival analysis
Catenacci D, Park H, Uronis H, Kang Y, Ng M, Enzinger P, Lee K, Lim K, Gold P, Lacy J, Park S, Huber K, Wynter-Horton A, Nordstrom J, Wu T, Wigginton J, Baughman J, Rosales M, Davidson-Moncada J, Bang Y. 1188PD Margetuximab (M) + pembrolizumab (P) for treatment of patients (pts) with HER2+ gastroesophageal adenocarcinoma (GEA) post-trastuzumab (T): Survival analysis. Annals Of Oncology 2019, 30: v484-v485. DOI: 10.1093/annonc/mdz253.014.Peer-Reviewed Original ResearchMedian progression-free survivalMedian overall survivalGenentech/RocheBristol-Myers SquibbGastroesophageal adenocarcinomaPD-L1Prime TherapeuticsOno PharmaceuticalOS ratesEMD SeronoMerck SeronoAstellas PharmaDaiichi SankyoGilead SciencesChemotherapy-free regimenPD-L1 CPSProgression-free survivalTreatment of patientsCancer ptsGuardant HealthMedian followMedian PFSCheckpoint inhibitorsExpansion cohortAcceptable tolerabilityAntitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC).
Catenacci D, Lim K, Uronis H, Kang Y, Ng M, Gold P, Enzinger P, Lee K, Lacy J, Park H, Yen J, Odegaard J, Franovic A, Baughman J, Wynter-Horton A, Chen F, Moore P, Wu T, Davidson-Moncada J, Bang Y. Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC). Journal Of Clinical Oncology 2019, 37: 65-65. DOI: 10.1200/jco.2019.37.4_suppl.65.Peer-Reviewed Original ResearchDisease control rateObjective response ratePD-L1 expressionGastric carcinomaHER2 expressionHigh PD-L1 expressionStandard first-line therapyTumor PD-L1 expressionChemo-free regimenDrug-related SAEsFirst-line therapyProgression-free survivalAnti-HER2 agentsAutoimmune hepatitisExploratory endpointsMedian overallDiabetic ketoacidosisAcceptable tolerabilityAdvanced HER2Adverse eventsPD-L1Control rateIHC 3Grade 3Archival tumors
2018
RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma.
Fuchs C, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran S, Van Cutsem E, Ilson D, Tabernero J, Chau I, Ducreux M, Mendez G, Molina Alavez A, Takahari D, Mansoor W, Lacy J, Gorbunova V, Ferry D, Lin J, Das M, Shah M. RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. Journal Of Clinical Oncology 2018, 36: 5-5. DOI: 10.1200/jco.2018.36.4_suppl.5.Peer-Reviewed Original ResearchProgression-free survivalFirst-line chemotherapyPrimary endpointITT populationOverall survivalPlacebo-controlled phase III studyECOG performance status 0Addition of ramucirumabIgG1 human monoclonal antibodiesPerformance status 0Powered secondary endpointSecond-line treatmentTreatment-naïve patientsFirst-line therapyNew safety signalsPhase III studyGastroesophageal junction adenocarcinomaSignificant clinical benefitHuman monoclonal antibodyImproved OSStatus 0Metastatic gastricSecondary endpointsAdverse eventsIII studyPhase II LAPACT trial of nab -paclitaxel ( nab -P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC).
Hammel P, Lacy J, Portales F, Sobrero A, Pazo Cid R, Manzano Mozo J, Terrebonne E, Dowden S, Shiansong Li J, Ong T, Nydam T, Philip P. Phase II LAPACT trial of nab -paclitaxel ( nab -P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC). Journal Of Clinical Oncology 2018, 36: 204-204. DOI: 10.1200/jco.2018.36.4_suppl.204.Peer-Reviewed Original ResearchProgression-free survivalDisease control rateOverall response rateTreatment failureAdverse eventsProgressive diseaseOverall survivalICS treatmentEastern Cooperative Oncology Group performance statusInvestigator's choiceGrade 3 peripheral neuropathyMedian progression-free survivalTreatment-emergent adverse eventsCycles of nabAdvanced pancreatic cancerKey secondary endpointMedian TTFTreatment-naive patientsPhase 2 trialUnacceptable adverse eventsPancreatic tumor burdenInduction therapyUnresectable LAPCInduction regimenNab-paclitaxel
2016
LAPACT: An open-label, multicenter phase II trial of nab -paclitaxel ( nab -P) plus gemcitabine (Gem) in patients (pts) with locally advanced pancreatic cancer (LAPC).
Philip P, Lacy J, Dowden S, Sastre J, Bathini V, Cardin D, Ma W, Sobrero A, Koski S, Borg C, Tonini G, Rivera F, Hwang J, Knoble J, Al Baghdadi T, Saif W, Meiri E, Kayitalire L, Li J, Hammel P. LAPACT: An open-label, multicenter phase II trial of nab -paclitaxel ( nab -P) plus gemcitabine (Gem) in patients (pts) with locally advanced pancreatic cancer (LAPC). Journal Of Clinical Oncology 2016, 34: tps477-tps477. DOI: 10.1200/jco.2016.34.4_suppl.tps477.Peer-Reviewed Original ResearchCycles of nabDisease control rateProgressive diseaseOverall survivalEastern Cooperative Oncology Group performance statusMulticenter phase II trialPhase III MPACT trialAdequate organ functionAdvanced pancreatic cancerCycles of therapySafety of nabEffective systemic therapyImproved local controlPhase II trialProgression-free survivalLonger overall survivalOverall response rateQuality of lifeMedian TTFMPACT trialSignificant ascitesUnresectable LAPCExploratory endpointsPrimary endpointSecondary endpoints