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 armPatients
2023
Atezolizumab 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 hyaluronidase
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
Antitumor 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
2017
Interim results of a multicenter phase II trial of nab -paclitaxel ( nab -P) plus gemcitabine (G) for patients (Pts) with locally advanced pancreatic cancer (LAPC).
Lacy J, Portales F, Hammel P, Pazo Cid R, Manzano Mozo J, Kim E, Dowden S, Borg C, Sastre J, Bathini V, Terrebonne E, Lopez-Trabada D, Rivera F, Asselah J, Damiani A, Hwang J, Ong T, Nydam T, Shiansong Li J, Philip P. Interim results of a multicenter phase II trial of nab -paclitaxel ( nab -P) plus gemcitabine (G) for patients (Pts) with locally advanced pancreatic cancer (LAPC). Journal Of Clinical Oncology 2017, 35: 358-358. DOI: 10.1200/jco.2017.35.4_suppl.358.Peer-Reviewed Original ResearchDisease control rateAdverse eventsMetastatic PCQOL scoresTreatment phaseDay 1Investigator's choiceMulticenter phase II trialInterim resultsCycles of nabECOG performance statusImproved symptom scoresQLQ-PAN26 questionnairesAdvanced pancreatic cancerG treatmentPhase II trialUnacceptable adverse eventsEORTC QLQ-C30Quality of lifeMPACT trialUnresectable LAPCII trialMost patientsNab-paclitaxelPerformance status