2024
A randomized phase 2 trial of the IO102-IO103 (IDO and PD-L1) cancer vaccine plus pembrolizumab as neoadjuvant/adjuvant treatment of patients with solid tumors.
Long G, Haddad R, Robert C, Mortier L, Schadendorf D, Uppaluri R, Svane I, Saiag P, Lim A, Soria Rivas A, Scolyer R, Chaney M, Abildgaard C, Ahmad Q, Ringeisen F, McDowell D, Burtness B. A randomized phase 2 trial of the IO102-IO103 (IDO and PD-L1) cancer vaccine plus pembrolizumab as neoadjuvant/adjuvant treatment of patients with solid tumors. Journal Of Clinical Oncology 2024, 42: tps2701-tps2701. DOI: 10.1200/jco.2024.42.16_suppl.tps2701.Peer-Reviewed Original ResearchEvent-free survivalAdjuvant pembrolizumabNeoadjuvant pembrolizumabCancer vaccinesAdjuvant treatmentCohort CCohort APD-L1-positive cellsRandomized phase 2 trialExpansion of T cellsPost-treatment tumor tissuesPotential anti-tumor activityImmune checkpoint inhibitorsResponse to pembrolizumabLocally advanced diseasePathologic tumor responseTherapeutic cancer vaccinesImmune-suppressive cellsPhase 1/2 trialDisease-free survivalNeo-adjuvant treatmentPhase 2 trialTreatment of multiple tumor typesSquamous cell carcinomaHead and neckCorrelative and spatial biomarker analysis of a phase 1/2b study to evaluate pepinemab in combination with pembrolizumab for first-line treatment of patients with recurrent or metastatic head and neck cancer.
Evans E, Fisher T, Mallow C, Foster A, Leonard J, Chaney M, Mekhail T, Seetharamu N, Steuer C, Saba N, Adkins D, Beck J, Algazi A, Burtness B, Baumgart M, Giampoli E, Hager S, Chay C, Spira A, Zauderer M. Correlative and spatial biomarker analysis of a phase 1/2b study to evaluate pepinemab in combination with pembrolizumab for first-line treatment of patients with recurrent or metastatic head and neck cancer. Journal Of Clinical Oncology 2024, 42: 2603-2603. DOI: 10.1200/jco.2024.42.16_suppl.2603.Peer-Reviewed Original ResearchHead and neck squamous cell carcinomaMyeloid suppressor cellsImmune checkpoint inhibitorsFirst-line treatmentDendritic cellsT cellsB cellsTumor biopsiesLymphoid structuresImmune cellsMetastatic head and neck squamous cell carcinomaActivity of immune checkpoint inhibitorsEfficacy of immune checkpoint inhibitorsSingle-arm open-label studyFirst-line treatment of patientsMetastatic head and neck cancerHead and neck squamous cell carcinoma tumorsImmune checkpoint inhibitor activationOn-treatment tumor biopsiesSuppression of adaptive immunityCD8+ T cellsNeck squamous cell carcinomaHead and neck cancerAnalysis of tumor biopsiesMechanism of immune enhancement
2023
Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma
Gavrielatou N, Vathiotis I, Aung T, Shafi S, Burela S, Fernandez A, Moutafi M, Burtness B, Economopoulou P, Anastasiou M, Foukas P, Psyrri A, Rimm D. Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma. Cancer Research Communications 2023, 3: 558-563. PMID: 37057033, PMCID: PMC10088911, DOI: 10.1158/2767-9764.crc-22-0299.Peer-Reviewed Original ResearchConceptsDigital spatial profilingB2M expressionOverall survivalM HNSCCImmunotherapy outcomesNeck squamous cell carcinoma (HNSCC) treatmentHigh beta-2 microglobulinSquamous cell carcinoma treatmentCell death protein 1Neck squamous cell carcinomaM expressionPretreatment biopsy samplesImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint markersDeath protein 1Squamous cell carcinomaB2MBeta-2-microglobulinBeta 2 microglobulin expressionImproved PFSCheckpoint inhibitorsMetastatic headCheckpoint markersImproved survival
2022
Phase 1/2 study of pepinemab, an inhibitor of semaphorin 4D, in combination with pembrolizumab as first-line treatment of recurrent or metastatic head and neck cancer (KEYNOTE-B84).
Fisher T, Evans E, Mallow C, Foster A, Boise M, Smith E, Leonard J, Chaney M, Beck J, Hager S, Mekhail T, Seetharamu N, Baumgart M, Saba N, Steuer C, Adkins D, Burtness B, Zauderer M. Phase 1/2 study of pepinemab, an inhibitor of semaphorin 4D, in combination with pembrolizumab as first-line treatment of recurrent or metastatic head and neck cancer (KEYNOTE-B84). Journal Of Clinical Oncology 2022, 40: e18033-e18033. DOI: 10.1200/jco.2022.40.16_suppl.e18033.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsFirst-line treatmentDose-expansion phaseM HNSCCComplete responsePD-L1Tumor microenvironmentClinical benefitSingle-arm open-label studyPrior immune checkpoint inhibitorsNeck squamous cell carcinomaSemaphorin 4DActivation of DCsExploratory biomarker analysisImmunosuppressive myeloid cellsTumor PD-L1Open-label studyPrimary efficacy endpointSquamous cell carcinomaPK/PDBiomarker analysisECOG 0Measurable diseaseTreatment biopsiesCheckpoint inhibitorsPhase 1/2 Study of Pepinemab in Combination with Pembrolizumab as First-Line Treatment of Advanced, Recurrent or Metastatic Head and Neck Cancer (KEYNOTE B84)
Fisher T, Evans E, Mallow C, Foster A, Boise M, Smith E, Leonard J, Chaney M, Beck J, Hager S, Saba N, Steuer C, Adkins D, Burtness B, Zauderer M. Phase 1/2 Study of Pepinemab in Combination with Pembrolizumab as First-Line Treatment of Advanced, Recurrent or Metastatic Head and Neck Cancer (KEYNOTE B84). International Journal Of Radiation Oncology • Biology • Physics 2022, 112: e36. DOI: 10.1016/j.ijrobp.2021.12.084.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsDose-expansion phaseFirst-line treatmentM HNSCCTumor microenvironmentPD-L1Clinical benefitT cellsSingle-arm open-label studyPrior immune checkpoint inhibitorsMore effective treatment optionsNeck squamous cell carcinomaActivation of DCsActivity of pembrolizumabExploratory biomarker analysisImmunosuppressive myeloid cellsTumor PD-L1Open-label studyPrimary efficacy endpointDuration of responseEffective treatment optionSquamous cell carcinomaClear unmet needPK/PDMore effective treatments
2020
Head and neck squamous cell carcinoma
Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nature Reviews Disease Primers 2020, 6: 92. PMID: 33243986, PMCID: PMC7944998, DOI: 10.1038/s41572-020-00224-3.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaSquamous cell carcinomaHuman papillomavirusCell carcinomaOral cavityLarynx cancerAJCC/UICC staging systemEGFR monoclonal antibody cetuximabLate stage HNSCCLeast toxic therapyImmune checkpoint inhibitorsHPV-positive HNSCCTreatment of recurrentHPV-positive diseaseOral cavity cancerUICC staging systemHPV-negative HNSCCPre-malignant lesionsDegree of dysplasiaMonoclonal antibody cetuximabUnresectable diseaseCheckpoint inhibitorsPrimary chemoradiotherapyCytotoxic chemotherapyMost patientsComparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer
Emancipator K, Huang L, Aurora-Garg D, Bal T, Cohen EEW, Harrington K, Soulières D, Le Tourneau C, Licitra L, Burtness B, Swaby R. Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer. Modern Pathology 2020, 34: 532-541. PMID: 33239737, DOI: 10.1038/s41379-020-00710-9.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyClinical Decision-MakingClinical Trials, Phase III as TopicDecision Support TechniquesDisease ProgressionHead and Neck NeoplasmsHumansImmunohistochemistryPredictive Value of TestsProgression-Free SurvivalRandomized Controlled Trials as TopicRetrospective StudiesSquamous Cell Carcinoma of Head and NeckTime FactorsConceptsTumor proportion scoreObjective response ratePD-L1 expression statusDeath ligand 1 (PD-L1) expressionNeck squamous cell carcinomaImmune checkpoint inhibitorsLigand 1 expressionPD-L1 statusProgression-free survivalSquamous cell carcinomaKEYNOTE-040Pembrolizumab efficacyCheckpoint inhibitorsOverall survivalMetastatic HNSCCCell carcinomaNeck cancerClinical trialsProportion scoreInvestigator's choiceResponse rateExpression statusYouden indexHNSCCPatientsKEYNOTE-048: Progression after the next line of therapy following pembrolizumab (P) or P plus chemotherapy (P+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Harrington K, Rischin D, Greil R, Soulieres D, Tahara M, Castro G, Psyrri A, Baste N, Neupane P, Bratland Å, Fuereder T, Hughes B, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak W, Zhang Y, Gumuscu B, Swaby R, Burtness B. KEYNOTE-048: Progression after the next line of therapy following pembrolizumab (P) or P plus chemotherapy (P+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Journal Of Clinical Oncology 2020, 38: 6505-6505. DOI: 10.1200/jco.2020.38.15_suppl.6505.Peer-Reviewed Original ResearchPD-L1 CPSSubsequent anticancer therapyM HNSCCMedian PFS2Subsequent therapyRecurrent/metastatic headNeck squamous cell carcinomaNext-line therapyObjective tumor progressionImmune checkpoint inhibitorsFirst-line therapyKaplan-Meier methodAnticancer therapySquamous cell carcinomaCox regression modelTotal populationKEYNOTE-048Superior OSCheckpoint inhibitorsMetastatic headSystemic therapyComparable safetyCell carcinomaFavorable safetyPatient outcomes
2019
The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)
Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, Le QT, Lee NY, Leidner R, Lewis RL, Licitra L, Mehanna H, Mell LK, Raben A, Sikora AG, Uppaluri R, Whitworth F, Zandberg DP, Ferris RL. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). Journal For ImmunoTherapy Of Cancer 2019, 7: 184. PMID: 31307547, PMCID: PMC6632213, DOI: 10.1186/s40425-019-0662-5.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaTreatment of patientsCell carcinomaNeck cancerAnti-PD-1 immune checkpoint inhibitorPD-L1 combined positive scoreMetastatic squamous cell carcinomaRecurrent squamous cell carcinomaApproval of nivolumabCancer consensus statementFirst new therapyImmune checkpoint inhibitorsPlatinum-based regimensPlatinum-containing chemotherapyRole of immunotherapyCombined positive scoreFirst-line treatmentPD-1 inhibitionTreatment of recurrentTumor proportion scoreAppropriate patient selectionAdverse event managementSame patient populationImmunotherapy of cancerCheckpoint inhibitorsHyperprogression after one dose of nivolumab in sinonasal cancer: A case report
Xiang JJ, Uy NF, Minja FJ, Verter EE, Burtness BA. Hyperprogression after one dose of nivolumab in sinonasal cancer: A case report. The Laryngoscope 2019, 130: 907-910. PMID: 31058321, DOI: 10.1002/lary.28042.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsDose of nivolumabSquamous cell carcinomaSinonasal cancerCell carcinomaDisease progressionMaxillary sinus squamous cell carcinomaSinus squamous cell carcinomaNeck squamous cell carcinomaComplete vision lossICI initiationCheckpoint inhibitorsFirst doseLytic metastasesDistal metastasisCase reportIntracranial invasionVision lossImproved outcomesHyperprogressionIndividual riskDoseNivolumabCarcinomaMetastasis