2024
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.
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 enhancementA phase 1 dose-escalation and expansion study of CUE-101, given as monotherapy and in combination with pembrolizumab, in patients with recurrent/metastatic HPV16+ head and neck squamous cell cancer (R/M HNSCC).
Colevas A, Chung C, Adkins D, Rodriguez C, Park J, Gibson M, Sukari A, Worden F, Johnson F, Saba N, Burtness B, Julian R, Bauman J, Jotte R, Seiwert T, Dunn L, Chaney M, Margossian S, Levisetti M, Pai S. A phase 1 dose-escalation and expansion study of CUE-101, given as monotherapy and in combination with pembrolizumab, in patients with recurrent/metastatic HPV16+ head and neck squamous cell cancer (R/M HNSCC). Journal Of Clinical Oncology 2024, 42: 6004-6004. DOI: 10.1200/jco.2024.42.16_suppl.6004.Peer-Reviewed Original ResearchCD8+ T cellsR/M HNSCCHuman leukocyte antigenT cellsMedian OSCheckpoint inhibitorsHLA-A*0201Adverse eventsInterleukin-2Combined cohortHead and neck squamous cell cancerE7-specific T cellsPhase 1 dose-escalationRecommended phase 2 doseTumor antigen-specific CD8First-in-human studyTargeted delivery of cytokinesHLA-A*0201 patientsPhase 2 doseDisease control rateGrade 3 AEsInfusion-related reactionsT-cell engagersSquamous cell cancerDelivery of cytokinesA Phase 1 Dose-escalation and Expansion Study of CUE-101, Given As Monotherapy in 3rd Line and in Combination with Pembrolizumab in 1st Line Recurrent/Metastatic (R/M) HPV16+ Head and Neck Cancer Patients
Colevas A, Chung C, Adkins D, Rodriguez C, Park J, Gibson M, Sukari A, Burtness B, Johnson F, Julian R, Saba N, Worden F, Dunn L, Seiwert T, Jotte R, Haddad R, Gabrail N, Bauman J, Margossian S, Pai S. A Phase 1 Dose-escalation and Expansion Study of CUE-101, Given As Monotherapy in 3rd Line and in Combination with Pembrolizumab in 1st Line Recurrent/Metastatic (R/M) HPV16+ Head and Neck Cancer Patients. International Journal Of Radiation Oncology • Biology • Physics 2024, 118: e87. DOI: 10.1016/j.ijrobp.2024.01.192.Peer-Reviewed Original ResearchCD8+ T cellsR/M HNSCCHuman leukocyte antigenT cellsHLA-A*0201Phase 1 dose-escalationTumor antigen-specific CD8First-in-human studyHead and neck cancer patientsTargeted delivery of cytokinesHLA-A*0201 patientsHPV16 E7 peptidesRecurrent/metastatic (R/MData cut-offInfusion-related reactionsT-cell engagersDelivery of cytokinesNeck cancer patientsTreatment of patientsPembrolizumab combinationDose escalationEscalating dosesComplete responseMaculopapular rashLeukocyte antigen
2023
Noncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors
Schrank T, Kothari A, Weir W, Stepp W, Rehmani H, Liu X, Wang X, Sewell A, Li X, Tasoulas J, Kim S, Yarbrough G, Xie Y, Flamand Y, Marur S, Hayward M, Wu D, Burtness B, Anderson K, Baldwin A, Yarbrough W, Issaeva N. Noncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2216532120. PMID: 37523561, PMCID: PMC10410762, DOI: 10.1073/pnas.2216532120.Peer-Reviewed Original ResearchConceptsNF-κB-related genesEstrogen receptor alpha expressionDeintensification of therapyTreatment-related morbidityTumor-infiltrating CD4Receptor alpha expressionHPV carcinogenesisRadiosensitization of headOncogenic subtypesPIK3CA alterationsHNSCC tumorsPatient outcomesNeck tumorsT cellsTreatment responseHNSCC cellsTherapeutic intensityAtypical featuresIndependent cohortAlpha expressionNF-κBActive tumorTNF receptorTumorsPatient data
2022
A phase 1 dose-escalation and expansion study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, given alone and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer.
Chung C, Colevas A, Adkins D, Gibson M, Rodriguez C, Sukari A, Bauman J, Wirth L, Johnson F, Saba N, Burtness B, Dunn L, Seiwert T, Worden F, Muzaffar J, Margossian S, Moniz R, Quayle S, Levisetti M, Pai S. A phase 1 dose-escalation and expansion study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, given alone and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer. Journal Of Clinical Oncology 2022, 40: 6045-6045. DOI: 10.1200/jco.2022.40.16_suppl.6045.Peer-Reviewed Original ResearchCD8+ T cellsHuman leukocyte antigenT cellsInterleukin-2R/M HNSCCHLA-A*0201Recurrent/metastatic head and neck squamous cell carcinomaTumor antigen-specific T cellsHead and neck squamous cell carcinomaDelivery of interleukin-2Phase 1 dose-escalationRecommended phase 2 doseTumor antigen-specific CD8Neck squamous cell carcinomaFirst-in-human studyAntitumor activityDose-escalation cohortsHLA-A*0201 patientsPhase 2 doseTumor-specific CD8Data cut-offSpecific T cellsFirst-line treatmentSquamous cell carcinomaDose-dependent increasePhase 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
2021
438 A phase 1 trial of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, alone and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer
Chung C, Colevas A, Gibson M, Adkins D, Sukari A, Wirth L, Burtness B, Bauman J, Rodriguez C, Worden F, Saba N, Glisson B, Dunn L, Seiwert T, Agensky L, Levisetti M, Lynam R, Margossian S, Moniz R, Quayle S, Pienta K, Pai S. 438 A phase 1 trial of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, alone and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer. Journal For ImmunoTherapy Of Cancer 2021, 9: a468-a468. DOI: 10.1136/jitc-2021-sitc2021.438.Peer-Reviewed Original ResearchTreatment of HPV16Institutional review boardT cellsCombination cohortInterleukin-2HPV16 E7-specific CD8HPV16-specific T cellsPD-L1 tumor expressionRecurrent/metastatic headTumor-specific T cellsNeck squamous cell carcinomaAntigen-specific T cell activationSpecific T cell activationCTCAE grade 2Ongoing partial responsePhase 2 doseRECIST 1.1 criteriaAntitumor activityE7-specific CD8First-line treatmentAnti-tumor immunityPost-treatment biopsiesNatural killer cellsPhase 1 trialSquamous cell carcinoma