2024
Pembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E
Chen E, Kavan P, Tehfe M, Kortmansky J, Sawyer M, Chiorean E, Lieu C, Polite B, Wong L, Fakih M, Spencer K, Chaves J, Li C, Leconte P, Adelberg D, Kim R. Pembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E. Clinical Colorectal Cancer 2024, 23: 183-193. PMID: 38653648, DOI: 10.1016/j.clcc.2024.03.002.Peer-Reviewed Original ResearchObjective response rateMetastatic colorectal cancerCohort ACohort CCohort EDose escalationInvestigator-assessed objective response rateColorectal cancerResponse rateModified toxicity probability interval designDose reductionSafety findingsPrimary endpointPembrolizumabBinimetinibLeucovorinE. CONCLUSIONSChemotherapyPatientsCohortIrinotecanOxaliplatinCancerInterval designWeeksPembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D
Kim R, Tehfe M, Kavan P, Chaves J, Kortmansky J, Chen E, Lieu C, Wong L, Fakih M, Spencer K, Zhao Q, Predoiu R, Li C, Leconte P, Adelberg D, Chiorean E. Pembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D. Clinical Colorectal Cancer 2024, 23: 118-127.e6. PMID: 38762348, DOI: 10.1016/j.clcc.2024.03.001.Peer-Reviewed Original ResearchMetastatic colorectal cancerObjective response rateCohort BCohort DAdverse eventsColorectal cancerT-cell-inflamed gene expression profileInvestigator-assessed objective response ratePD-L1 combined positive scoreTreatment-related adverse eventsResponse rateCombined positive scoreDose-limiting toxicityMedian follow-upTumor mutational burdenDecreased neutrophil countPrimary end pointMismatch repair-proficientStandard of careBiomarker analysisMethods PatientsRECIST v1.1PD-L1HER2 expressionMutational burden
2023
Quantitative 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 markers
2022
Pembrolizumab (pembro) plus binimetinib (bini) with or without chemotherapy (chemo) for metastatic colorectal cancer (mCRC): Results from KEYNOTE-651 cohorts A, C, and E.
Chen E, Kavan P, Tehfe M, Kortmansky J, Sawyer M, Chiorean E, Lieu C, Polite B, Wong L, Fakih M, Spencer K, Chaves J, Li C, Carpenter D, Leconte P, Kim R. Pembrolizumab (pembro) plus binimetinib (bini) with or without chemotherapy (chemo) for metastatic colorectal cancer (mCRC): Results from KEYNOTE-651 cohorts A, C, and E. Journal Of Clinical Oncology 2022, 40: 3573-3573. DOI: 10.1200/jco.2022.40.16_suppl.3573.Peer-Reviewed Original ResearchMetastatic colorectal cancerDose-limiting toxicityCohort ACohort ECohort CEvaluable ptsMicrosatellite stableDose levelsEnd pointDose-finding phasePrimary end pointSecondary end pointsKRAS mutation statusTotal PtCohort A.RECIST v1.1Data cutoffMulticenter trialDose escalationColorectal cancerMedian studyPembroDose reductionLimited efficacyTRAEsPembrolizumab (pembro) plus mFOLFOX7 or FOLFIRI for metastatic colorectal cancer (CRC) in KEYNOTE-651: Long-term follow-up of cohorts B and D.
Kim R, Tehfe M, Kavan P, Chaves J, Kortmansky J, Chen E, Lieu C, Wong L, Fakih M, Spencer K, Zhao Q, Predoiu R, Li C, Carpenter D, Leconte P, Chiorean E. Pembrolizumab (pembro) plus mFOLFOX7 or FOLFIRI for metastatic colorectal cancer (CRC) in KEYNOTE-651: Long-term follow-up of cohorts B and D. Journal Of Clinical Oncology 2022, 40: 3521-3521. DOI: 10.1200/jco.2022.40.16_suppl.3521.Peer-Reviewed Original ResearchCohort BColorectal cancerCohort DPMMR colorectal cancerRECIST v1.1End pointExploratory end pointsPD-L1 dataSingle-arm cohortAntitumor activityManageable safety profileMetastatic colorectal cancerPrimary end pointSecondary end pointsNew safety signalsAntitumor immune responseCombination of chemotherapyKRAS mutation statusGreater antitumor activityData cutoffStarting doseNeutrophil countPrior linesInvestigator reviewSafety profile
2020
A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer
Cecchini M, Kortmansky JS, Cui C, Wei W, Thumar JR, Uboha NV, Hafez N, Lacy J, Fischbach NA, Sabbath KD, Gomez CM, Sporn JR, Stein S, Hochster HS. A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer. Cancer 2020, 127: 1417-1424. PMID: 33351187, PMCID: PMC8085021, DOI: 10.1002/cncr.33379.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsDrug Administration ScheduleDrug CombinationsDrug Resistance, NeoplasmFemaleFluorouracilHumansIrinotecanLeucovorinMaleMiddle AgedOrganoplatinum CompoundsOxaliplatinProgression-Free SurvivalPyrrolidinesResponse Evaluation Criteria in Solid TumorsThymineTrifluridineConceptsMetastatic colorectal cancerOverall response rateRefractory metastatic colorectal cancerProgression-free survivalTAS-102Colorectal cancerDay 1Primary endpointOverall survivalDose escalationDay 5Median progression-free survivalPhase 1b studyMedian overall survivalResponse Evaluation CriteriaTreat populationDose expansionPartial responseStandard dosesUnexpected side effectsStudy treatmentTumor shrinkageUnexpected toxicitiesSide effectsNovel antimetabolitePembrolizumab (pembro) plus mFOLFOX7 or FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC): Updated results from KEYNOTE-651 cohorts B and D
Kim R, Chaves J, Kavan P, Fakih M, Kortmansky J, Spencer K, Wong L, Tehfe M, Li J, Eyring A, Mayo C, Chiorean E. Pembrolizumab (pembro) plus mFOLFOX7 or FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC): Updated results from KEYNOTE-651 cohorts B and D. Annals Of Oncology 2020, 31: s450. DOI: 10.1016/j.annonc.2020.08.604.Peer-Reviewed Original Research
2019
608P Pembrolizumab (pembro) plus mFOLFOX or FOLFIRI in patients with metastatic colorectal cancer (mCRC): KEYNOTE-651 cohorts B and D
Kim R, Chaves J, Kavan P, Fakih M, Kortmansky J, Spencer K, Wong L, Tehfe M, Li J, Lee M, Mayo C, Marinello P, Chiorean E. 608P Pembrolizumab (pembro) plus mFOLFOX or FOLFIRI in patients with metastatic colorectal cancer (mCRC): KEYNOTE-651 cohorts B and D. Annals Of Oncology 2019, 30: v229-v230. DOI: 10.1093/annonc/mdz246.085.Peer-Reviewed Original ResearchMetastatic colorectal cancerTreatment-related AEsSubsidiary of MerckCohort BCohort DDohme Corp.Merck SharpEastern Cooperative Oncology Group performance status 0/1Stage IV metastatic colorectal cancerArray BioPharmaOxaliplatin-based regimenPerformance status 0/1Phase 2 dosePrior systemic chemotherapySafety/tolerabilityObjective response ratePD-1 inhibitorsDose-limiting toxicitySmall intestinal obstructionData cutoffImmunotherapy agentsSystemic chemotherapyMethods PatientsColorectal cancerEMD SeronoAtezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial
Eng C, Kim T, Bendell J, Argilés G, Tebbutt N, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal N, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F, Investigators I, Ahn J, Asselah J, Badarinath S, Baijal S, Begbie S, Berry S, Canon J, Carbone R, Cervantes A, Cha Y, Chang K, Chaudhry A, Chmielowska E, Cho S, Chu D, Couture F, Cultrera J, Cunningham D, Van Cutsem E, Cuyle P, Davies J, Dowden S, Dvorkin M, Ganju V, Garcia R, Kerr R, Kim T, King K, Kortmansky J, Kozloff M, Lam K, Lee J, Lee A, Lesperance B, Luppi G, Ma B, Maiello E, Mandanas R, Marshall J, Marx G, Mullamitha S, Nechaeva M, Park J, Pavlakis N, Ponce C, Potemski P, Raouf S, Reeves J, Segal N, Siena S, Smolin A, Streb J, Strickland A, Szutowicz-Zielinska E, Tabernero J, Tan B, Valera J, Van den Eynde M, Vergauwe P, Vickers M, Womack M, Wroblewska M, Young R. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. The Lancet Oncology 2019, 20: 849-861. PMID: 31003911, DOI: 10.1016/s1470-2045(19)30027-0.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerMicrosatellite-stable metastatic colorectal cancerRegorafenib groupOverall survivalColorectal cancerAdverse eventsCombination groupAtezolizumab groupAtezolizumab monotherapyOpen-labelBaseline Eastern Cooperative Oncology Group performance statusEndpoint of improving overall survivalEastern Cooperative Oncology Group performance statusAll-cause grade 3Increased blood creatine phosphokinaseTreat metastatic colorectal cancerIntention-to-treat populationControlled trialsSafety of atezolizumabSystemic chemotherapy regimensThird-line settingMedian overall survivalTreatment-related deathsImmunotherapy to patientsMedian follow-upA phase I study of TAS-102 in combination with oxaliplatin (TAS-OX) for refractory metastatic colorectal cancer (mCRC).
Cecchini M, Kortmansky J, Lacy J, Fischbach N, Thumar J, Sabbath K, Gomez C, Sporn J, Stein S, Hochster H. A phase I study of TAS-102 in combination with oxaliplatin (TAS-OX) for refractory metastatic colorectal cancer (mCRC). Journal Of Clinical Oncology 2019, 37: 630-630. DOI: 10.1200/jco.2019.37.4_suppl.630.Peer-Reviewed Original ResearchDisease control rateMetastatic colorectal cancerTAS-102Progressive diseaseDay 1Thymidine phosphorylase inhibitorRefractory metastatic colorectal cancerDose-escalating studyECOG PS 0Phase II doseEfficacy of oxaliplatinUsual laboratory parametersEligible patientsEvaluable patientsMeasurable diseaseUnexpected AEsStarting doseTreatment discontinuationPS 0Improved survivalLaboratory parametersOral combinationColorectal cancerPatient populationControl rate