2024
CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors
Skoulidis F, Araujo H, Do M, Qian Y, Sun X, Cobo A, Le J, Montesion M, Palmer R, Jahchan N, Juan J, Min C, Yu Y, Pan X, Arbour K, Vokes N, Schmidt S, Molkentine D, Owen D, Memmott R, Patil P, Marmarelis M, Awad M, Murray J, Hellyer J, Gainor J, Dimou A, Bestvina C, Shu C, Riess J, Blakely C, Pecot C, Mezquita L, Tabbó F, Scheffler M, Digumarthy S, Mooradian M, Sacher A, Lau S, Saltos A, Rotow J, Johnson R, Liu C, Stewart T, Goldberg S, Killam J, Walther Z, Schalper K, Davies K, Woodcock M, Anagnostou V, Marrone K, Forde P, Ricciuti B, Venkatraman D, Van Allen E, Cummings A, Goldman J, Shaish H, Kier M, Katz S, Aggarwal C, Ni Y, Azok J, Segal J, Ritterhouse L, Neal J, Lacroix L, Elamin Y, Negrao M, Le X, Lam V, Lewis W, Kemp H, Carter B, Roth J, Swisher S, Lee R, Zhou T, Poteete A, Kong Y, Takehara T, Paula A, Parra Cuentas E, Behrens C, Wistuba I, Zhang J, Blumenschein G, Gay C, Byers L, Gibbons D, Tsao A, Lee J, Bivona T, Camidge D, Gray J, Leighl N, Levy B, Brahmer J, Garassino M, Gandara D, Garon E, Rizvi N, Scagliotti G, Wolf J, Planchard D, Besse B, Herbst R, Wakelee H, Pennell N, Shaw A, Jänne P, Carbone D, Hellmann M, Rudin C, Albacker L, Mann H, Zhu Z, Lai Z, Stewart R, Peters S, Johnson M, Wong K, Huang A, Winslow M, Rosen M, Winters I, Papadimitrakopoulou V, Cascone T, Jewsbury P, Heymach J. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature 2024, 635: 462-471. PMID: 39385035, PMCID: PMC11560846, DOI: 10.1038/s41586-024-07943-7.Peer-Reviewed Original ResearchNon-small-cell lung cancerImmune checkpoint blockadeTumor suppressor genePD-L1Advanced non-small-cell lung cancerCD8+ cytotoxic T cellsSuppressor geneCD4+ effector cellsDual immune checkpoint blockadeMouse modelPD-L1 inhibitor durvalumabSuppressive myeloid cellsPD-L1 inhibitorsImmune-related toxicitiesPD-(L)1 inhibitorsAnti-tumor efficacyCytotoxic T cellsMyeloid cell compartmentAdverse tumor microenvironmentAssociated with higher ratesAnti-tumor activityLoss of Keap1CTLA4 inhibitorsSTK11 alterationsCheckpoint blockade
2020
SWOG S1400F (NCT03373760): A phase II study of durvalumab plus tremelimumab for previously treated patients with acquired resistance to PD-1 checkpoint inhibitor therapy and stage IV squamous cell lung cancer (Lung-MAP Sub-study).
Leighl N, Redman M, Rizvi N, Hirsch F, Mack P, Schwartz L, Wade J, Irvin W, Reddy S, Crawford J, Bradley J, Stinchcombe T, Ramalingam S, Miao J, Minichiello K, Gandara D, Herbst R, Papadimitrakopoulou V, Kelly K. SWOG S1400F (NCT03373760): A phase II study of durvalumab plus tremelimumab for previously treated patients with acquired resistance to PD-1 checkpoint inhibitor therapy and stage IV squamous cell lung cancer (Lung-MAP Sub-study). Journal Of Clinical Oncology 2020, 38: 9623-9623. DOI: 10.1200/jco.2020.38.15_suppl.9623.Peer-Reviewed Original ResearchSquamous lung carcinomaLung carcinomaMedian PFSAdverse eventsObjective responseDisease progressionStage IV squamous cell lung cancerPD-1 checkpoint inhibitor therapySquamous cell lung cancerPD-1 checkpoint inhibitorsGood responseAdequate organ functionGrade 4 dyspneaPerformance status 0PR/SDTreatment-related deathsCheckpoint inhibitor therapyImmune-related toxicitiesPhase II studyPD-1 inhibitionBest objective responseCell lung cancerEligible patientsQ28 daysStatus 0
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