2025
A randomized phase 3 study of ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of metastatic non–small cell lung cancer: HARMONi-3.
Zhang J, Cai J, Wang H, Yu Y, Bosch-Barrera J, Bernabé R, Andric Z, Badin F, Okuma Y, Paik P, Naidoo J, Kalofonos H, Wang B, Jotte R, Pennell N, Riess J, Doroshow D, Nishio M, Alatorre-Alexander J, Lu S. A randomized phase 3 study of ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of metastatic non–small cell lung cancer: HARMONi-3. Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.tps8664.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalFirst-line treatmentMetastatic non-small cell lung cancerCell lung cancerPD-1PD-L1Metastatic diseaseFirst-line treatment of metastatic non-small cell lung cancerLung cancerPD-L1 tumor proportion scoreTreatment of metastatic non-small cell lung cancerProgrammed cell death protein 1Cell death protein 1Programmed death-ligand 1Randomized phase 3 studyStandard first-line treatmentDevelopment of metastatic diseaseDisease control rateTumor proportion scoreDeath-ligand 1Platinum-doublet chemotherapyTargeting PD-1Duration of responseFirst-line therapyFirst-line immunotherapy with or without chemotherapy versus BRAF plus MEK inhibitors for patients with BRAF V600E -mutated metastatic non-small cell lung cancer: The FRONT-BRAF study.
Di Federico A, Wang K, Chen M, Barsouk A, Pagliaro A, Chen L, Ogliari F, Stockhammer P, Thawani R, Raslan S, Gariazzo E, Fusco F, Hambelton G, Citarella F, Meyer D, Corassa M, Langer C, Offin M, Negrao M, Ricciuti B. First-line immunotherapy with or without chemotherapy versus BRAF plus MEK inhibitors for patients with BRAF V600E -mutated metastatic non-small cell lung cancer: The FRONT-BRAF study. Journal Of Clinical Oncology 2025, 43: 8574-8574. DOI: 10.1200/jco.2025.43.16_suppl.8574.Peer-Reviewed Original ResearchTP53 co-mutationsTumor proportion scoreShorter mPFSCo-mutationsBRAF V600EMEK inhibitorsPD-L1 tumor proportion scoreMetastatic non-small cell lung cancerNon-small cell lung cancerHistory of tobacco smokingFirst-line immunotherapyMedian overall survivalSubgroups of ptsTreated with BRAFProgression-free survivalRate of adverse eventsWild-type TP53Cell lung cancerHistory of smokingTobacco smoking historyScore-matched cohortWild-type IDH1PD-L1Brain metastasesLine therapy
2024
Lenvatinib ± Pembrolizumab Versus Chemotherapy for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That Progressed after Platinum and Immunotherapy: The Phase 2 LEAP-009 Study
Harrington K, Kim H, Salas S, Oliva M, Metcalf R, Bernsdorf M, Kim J, Cohen E, Siu L, Rischin D, Licitra L, Vermorken J, Le Q, Tahara M, Machiels J, O'Hara K, Pathiraja K, Gumuscu B, Bidadi B, Burtness B. Lenvatinib ± Pembrolizumab Versus Chemotherapy for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That Progressed after Platinum and Immunotherapy: The Phase 2 LEAP-009 Study. International Journal Of Radiation Oncology • Biology • Physics 2024, 118: e42. DOI: 10.1016/j.ijrobp.2024.01.095.Peer-Reviewed Original ResearchR/M HNSCCHead and neck squamous cell carcinomaPD-1/L1 inhibitorsPlatinum-based therapyPlatinum-based chemotherapyDisease progressionLenvatinib monotherapyECOG PSRecurrent/metastatic (R/M) head and neck squamous cell carcinomaPD-L1 tumor proportion scoreStandard-of-care chemotherapyNeck squamous cell carcinomaTumor proportion scoreProgression-free survivalDuration of responseEfficacy of lenvatinibSecondary end pointsFirst-line treatmentSquamous cell carcinomaEfficacious treatment optionStandard of careOral lenvatinibPembrolizumab monotherapyRECIST v1.1Monotherapy arm
2023
Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC ☆
Mok T, Lopes G, Cho B, Kowalski D, Kasahara K, Wu Y, de Castro G, Turna H, Cristescu R, Aurora-Garg D, Loboda A, Lunceford J, Kobie J, Ayers M, Pietanza M, Piperdi B, Herbst R. Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC ☆. Annals Of Oncology 2023, 34: 377-388. PMID: 36709038, DOI: 10.1016/j.annonc.2023.01.011.Peer-Reviewed Original ResearchConceptsTissue tumor mutational burdenImproved overall survivalProgression-free survivalTumor mutational burdenOverall survivalKEYNOTE-042Pembrolizumab monotherapyKRAS mutationsClinical utilityMutational burdenMutation statusPD-L1 tumor proportion scoreStandard first-line treatmentEGFR/ALK alterationsAdvanced PD-L1First-line treatmentPD-L1 expressionTumor proportion scorePlatinum-based chemotherapyDeath ligand 1Cell lung cancerPotential predictive biomarkersCut pointsKRAS mutation statusRetrospective exploratory analysis
2022
Phase 2 LEAP-009: Lenvatinib (Lenva) With or Without Pembrolizumab (Pembro) vs. Chemotherapy (Chemo) for Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That has Progressed on Platinum and Immunotherapy
Harrington K, Cohen E, Siu L, Rischin D, Licitra L, Vermorken J, Le Q, Tahara M, Machiels J, Hawk N, Ge J, Bidadi B, Swaby R, Burtness B. Phase 2 LEAP-009: Lenvatinib (Lenva) With or Without Pembrolizumab (Pembro) vs. Chemotherapy (Chemo) for Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That has Progressed on Platinum and Immunotherapy. International Journal Of Radiation Oncology • Biology • Physics 2022, 112: e43-e44. DOI: 10.1016/j.ijrobp.2021.12.101.Peer-Reviewed Original ResearchPD-1/PD-L1 inhibitorsECOG performance statusPD-L1 inhibitorsM HNSCCDisease progressionRECIST v1.1Monotherapy armPerformance statusPO QDPD-L1 tumor proportion scoreOptimal second-line regimenEnd pointNeck squamous cell carcinomaPrimary end pointSecond-line regimenSecondary end pointsFirst-line treatmentTumor proportion scoreKey eligibility criteriaSquamous cell carcinomaInterim futility analysisMeasurable diseaseSOC chemotherapyMetastatic headUnacceptable toxicityAssociation of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer
Gavrielatou N, Liu Y, Vathiotis I, Zugazagoitia J, Aung TN, Shafi S, Fernandez A, Schalper K, Psyrri A, Rimm DL. Association of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer. Clinical Cancer Research 2022, 28: clincanres.2649.2021. PMID: 34686497, PMCID: PMC8776595, DOI: 10.1158/1078-0432.ccr-21-2649.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerBest overall responsePD-L1 tumor proportion scorePD-1/PD-L1Immune checkpoint inhibitorsProgression-free survivalTumor proportion scoreCell lung cancerPD-L1Immunotherapy outcomesCheckpoint inhibitorsOverall survivalQuantitative immunofluorescenceLung cancerProportion scoreAdvanced non-small cell lung cancerLocal T cell responsesCell death protein 1Immunotherapy-treated patientsMultiplexed quantitative immunofluorescencePD-1 expressionPD-L1 expressionDeath protein 1Selection of patientsT cell responses
2021
Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC
Doroshow DB, Wei W, Gupta S, Zugazagoitia J, Robbins C, Adamson B, Rimm DL. Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC. Journal Of Thoracic Oncology 2021, 16: 2139-2143. PMID: 34455068, PMCID: PMC8612948, DOI: 10.1016/j.jtho.2021.07.032.Peer-Reviewed Original ResearchConceptsPD-L1 tumor proportion scoreTumor proportion scoreHigh PD-L1 tumor proportion scoreOverall survivalNonsquamous histologySquamous NSCLCNonsquamous NSCLCPredictive biomarkersProportion scoreDeath ligand 1 (PD-L1) tumor proportion scoreElectronic health record-derived databaseFirst-line pembrolizumab therapyPD-1 expression levelsPD-L1 expression levelsCommunity oncology clinicsMedian OS differenceSingle-agent pembrolizumabImmune checkpoint inhibitorsImproved overall survivalMedian overall survivalPrimary end pointFirst-line pembrolizumabFirst-line therapyPD-L1 expressionPD-L1 testingFive Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC
Herbst RS, Garon EB, Kim DW, Cho BC, Gervais R, Perez-Gracia JL, Han JY, Majem M, Forster MD, Monnet I, Novello S, Gubens MA, Boyer M, Su WC, Samkari A, Jensen EH, Kobie J, Piperdi B, Baas P. Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC. Journal Of Thoracic Oncology 2021, 16: 1718-1732. PMID: 34048946, DOI: 10.1016/j.jtho.2021.05.001.Peer-Reviewed Original ResearchConceptsPD-L1 tumor proportion scoreTumor proportion scoreAdvanced NSCLCOverall survivalPembrolizumab improved overall survivalTissue tumor mutational burdenExploratory biomarker analysisImproved overall survivalProgrammed Death LigandTumor mutational burdenDocetaxel 75KEYNOTE-010Pembrolizumab dosesPembrolizumab treatmentSurvival updateData cutoffObjective responseHazard ratioOS ratesCare treatmentLong-term benefitsMedian studyImproved outcomesPembrolizumabProportion score
2020
351 Pembrolizumab plus lenvatinib vs chemotherapy and lenvatinib monotherapy for recurrent/metastatic head and neck squamous cell carcinoma that progressed on platinum therapy and immunotherapy: LEAP-009
Harrington K, Cohen E, Siu L, Rischin D, Licitra L, Vermorken J, Le Q, Tahara M, Machiels J, Hawk N, Ge J, Bidadi B, Swaby R, Burtness B. 351 Pembrolizumab plus lenvatinib vs chemotherapy and lenvatinib monotherapy for recurrent/metastatic head and neck squamous cell carcinoma that progressed on platinum therapy and immunotherapy: LEAP-009. Journal For ImmunoTherapy Of Cancer 2020, 8: a376-a376. DOI: 10.1136/jitc-2020-sitc2020.0351.Peer-Reviewed Original ResearchPlatinum-based chemotherapyRecurrent/metastatic headNeck squamous cell carcinomaECOG performance statusSquamous cell carcinomaDisease progressionLenvatinib monotherapyM HNSCCCell carcinomaRECIST v1.1SOC chemotherapyMetastatic headMonotherapy armPerformance statusTreatment optionsPhase Ib/II trialStandard first-line treatment optionPD-L1 tumor proportion scoreFirst-line treatment optionAdvanced renal cell carcinomaJ Clin OncolSafety of pembrolizumabPD-1 inhibitorsPlatinum-containing chemotherapyAdvanced solid tumorsPhase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC
Herbst RS, Arkenau HT, Bendell J, Arrowsmith E, Wermke M, Soriano A, Penel N, Santana-Davila R, Bischoff H, Chau I, Mi G, Wang H, Rasmussen E, Ferry D, Chao BH, Paz-Ares L. Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Journal Of Thoracic Oncology 2020, 16: 289-298. PMID: 33068794, DOI: 10.1016/j.jtho.2020.10.004.Peer-Reviewed Original ResearchConceptsProgression-free survivalTumor proportion scoreMedian progression-free survivalTreatment-related adverse eventsPD-L1 expressionT-cell signatureCD274 gene expressionAdverse eventsPhase 1a/b trialPD-L1 tumor proportion scoreHigh PD-L1 expressionManageable safety profileMedian overall survivalObjective response ratePD-L1 positivityFirst-line therapyOverall survival ratePD-L1 immunohistochemistryCohort EPembrolizumab treatmentPFS ratesExpansion cohortClinical responseOverall survivalEfficacy signalsPD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous non-small cell lung cancer (NSCLC).
Doroshow D, Wei W, Zugazagoitia J, Robbins C, Gupta S, Adamson B, Rimm D. PD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2020, 38: 9539-9539. DOI: 10.1200/jco.2020.38.15_suppl.9539.Peer-Reviewed Original ResearchPD-L1 tumor proportion scoreNon-small cell lung cancerTumor proportion scoreMedian overall survivalFirst-line pembrolizumabOverall survivalLonger OSHazard ratioPD-L1Predictive biomarkersNS patientsProportion scoreSquamous non-small cell lung cancerAppropriate predictive biomarkersUnadjusted hazard ratioNSCLC tumor cellsLonger overall survivalCell lung cancerCheckpoint inhibitor useDe-identified databaseHistology interactionNonsquamous cancerSQ patientsSquamous histologyPrimary endpointTrial in progress: A phase I/II, open-label, dose-escalation, safety and tolerability study of NC318 in subjects with advanced or metastatic solid tumors.
Gutierrez M, Hamid O, Shum E, Wise D, Balar A, Weber J, LoRusso P, Shafi S, Rimm D, Tolcher A, Basudhar D, Dujka M, Heller K. Trial in progress: A phase I/II, open-label, dose-escalation, safety and tolerability study of NC318 in subjects with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2020, 38: tps3166-tps3166. DOI: 10.1200/jco.2020.38.15_suppl.tps3166.Peer-Reviewed Original ResearchMetastatic solid tumorsT cell functionSolid tumorsPD-L1 tumor proportion scoreAnti-tumor immune responseNon-small cell lungPhase I/IIPhase 2 doseTumor proportion scoreAnti-tumor immunityKey eligibility criteriaCell functionDose-escalation designBreast cancer subjectsNon-randomized studiesT cell proliferationPrevents tumor growthClass monoclonal antibodyCollection of biopsiesMeasurable diseaseRECIST v1.1Phase 1/2Escalation designTolerability studyImmune suppressionTumour cell PD-L1 expression is prognostic in patients with malignant pleural effusion: the impact of C-reactive protein and immune-checkpoint inhibition
Ghanim B, Rosenmayr A, Stockhammer P, Vogl M, Celik A, Bas A, Kurul IC, Akyurek N, Varga A, Plönes T, Bankfalvi A, Hager T, Schuler M, Hackner K, Errhalt P, Scheed A, Seebacher G, Hegedus B, Stubenberger E, Aigner C. Tumour cell PD-L1 expression is prognostic in patients with malignant pleural effusion: the impact of C-reactive protein and immune-checkpoint inhibition. Scientific Reports 2020, 10: 5784. PMID: 32238865, PMCID: PMC7113285, DOI: 10.1038/s41598-020-62813-2.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionC-reactive proteinMalignant pleural effusionKi-67 indexPD-L1Overall survivalPleural effusionPrognostic powerPD-L1 tumor proportion scoreNegative PD-L1 statusPD-L1 positive tumorsLonger median OSMedian overall survivalPD-L1 expressionPD-L1 statusTumor proportion scoreFurther prospective validationVariety of malignanciesICI therapyMedian OSSignificant prognosticatorShorter OSIndependent prognosticatorPrognostic roleDismal prognosisLong-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study.
Herbst RS, Garon EB, Kim DW, Cho BC, Perez-Gracia JL, Han JY, Arvis CD, Majem M, Forster MD, Monnet I, Novello S, Szalai Z, Gubens MA, Su WC, Ceresoli GL, Samkari A, Jensen EH, Lubiniecki GM, Baas P. Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study. Journal Of Clinical Oncology 2020, 38: 1580-1590. PMID: 32078391, DOI: 10.1200/jco.19.02446.Peer-Reviewed Original ResearchConceptsTumor proportion scoreTreatment-related adverse eventsSecond-course treatmentOverall survivalAdverse eventsLung cancerGrade 3Advanced non-small cell lung cancerPD-L1 tumor proportion scoreNon-small cell lung cancerLong-term OS benefitPembrolizumab improved overall survivalProgression-free survival ratesProgrammed Death Ligand 1Improved overall survivalDeath ligand 1Cell lung cancerLong-term outcomesYears of treatmentOS benefitPembrolizumab dosesStable diseaseAdvanced NSCLCEligible patientsDurable responses
2019
Randomized, double-blind, phase 3 trial of first-line pembrolizumab + platinum doublet chemotherapy (chemo) ± lenvatinib in patients (pts) with metastatic nonsquamous non–small-cell lung cancer (NSCLC): LEAP-006.
Hui R, Nishio M, Reck M, Rodriguez-Abreu D, Fouad T, Flaim D, Yin L, Dang T, Herbst R. Randomized, double-blind, phase 3 trial of first-line pembrolizumab + platinum doublet chemotherapy (chemo) ± lenvatinib in patients (pts) with metastatic nonsquamous non–small-cell lung cancer (NSCLC): LEAP-006. Journal Of Clinical Oncology 2019, 37: tps9118-tps9118. DOI: 10.1200/jco.2019.37.15_suppl.tps9118.Peer-Reviewed Original ResearchPrimary endpointPD-L1 tumor proportion scoreFirst-line lenvatinibMetastatic nonsquamous NSCLCNCI CTCAE v4.0Platinum-doublet chemotherapyFirst-line pembrolizumabPhase 3 trialTumor proportion scoreDose-limiting toxicityKaplan-Meier methodCell lung cancerLog-rank testQuality of lifeDoublet chemotherapyECOG PSMaintenance pembrolizumabAdvanced NSCLCNonsquamous NSCLCSecondary endpointsStudy withdrawalCTCAE v4.0Carboplatin AUCNew cancer therapiesLung cancerUse of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial
Herbst RS, Baas P, Perez-Gracia JL, Felip E, Kim D, Han J, Molina JR, Kim J, Arvis C, Ahn M, Majem M, Fidler MJ, Surmont V, de Castro G, Garrido M, Shentu Y, Emancipator K, Samkari A, Jensen EH, Lubiniecki GM, Garon EB. Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Annals Of Oncology 2019, 30: 281-289. PMID: 30657853, PMCID: PMC6931268, DOI: 10.1093/annonc/mdy545.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiopsyCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDocetaxelFemaleFollow-Up StudiesHumansInternational AgenciesLung NeoplasmsMaleMiddle AgedParaffin EmbeddingPrognosisSpecimen HandlingSurvival RateYoung AdultConceptsTumor proportion scoreOS hazard ratioPD-L1 expressionProgression-free survivalPFS hazard ratioHazard ratioOverall survivalTumor samplesPD-L1PD-L1 tumor proportion scorePrespecified exploratory analysisPrimary end pointSubset of patientsCell lung cancerDeath 1 proteinArchival samplesDocetaxel 75KEYNOTE-010Pembrolizumab dosesRECIST v1.1Advanced NSCLCLung cancerProportion scorePatientsPrimary analysis
2016
Pembrolizumab vs docetaxel for previously treated advanced NSCLC with a PD-L1 tumor proportion score (TPS) 1%-49%: Results from KEYNOTE-010.
Garon E, Herbst R, Kim D, Felip E, Perez-Gracia J, Han J, Molina J, Kim J, Dubos Arvis C, Ahn M, Majem M, Fidler M, Gubens M, Castro G, Garrido M, Shentu Y, Im E, Lubiniecki G, Baas P. Pembrolizumab vs docetaxel for previously treated advanced NSCLC with a PD-L1 tumor proportion score (TPS) 1%-49%: Results from KEYNOTE-010. Journal Of Clinical Oncology 2016, 34: 9024-9024. DOI: 10.1200/jco.2016.34.15_suppl.9024.Peer-Reviewed Original ResearchTumor proportion scorePD-L1 tumor proportion scoreKEYNOTE-010Advanced NSCLCProportion scoreNSCLCDocetaxel
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