2025
S1900E: A phase II study examining impact of co-mutations on sotorasib for previously treated stage IV/recurrent KRAS G12C mutated (MUT) non-squamous (Non-sq) non-small cell lung cancer (NSCLC) (ECOG-ACRIN led Lung-MAP Sub-study).
Padda S, Redman M, Gerber D, Minichiello K, Mehta D, Mashru S, Hakim H, Brahmer J, Bradley J, Stinchcombe T, Gray J, Kelly K, Kozono D, Reckamp K, Edelman M, Borghaei H, Patel J, Herbst R, Ramalingam S, Neal J. S1900E: A phase II study examining impact of co-mutations on sotorasib for previously treated stage IV/recurrent KRAS G12C mutated (MUT) non-squamous (Non-sq) non-small cell lung cancer (NSCLC) (ECOG-ACRIN led Lung-MAP Sub-study). Journal Of Clinical Oncology 2025, 43: 8518-8518. DOI: 10.1200/jco.2025.43.16_suppl.8518.Peer-Reviewed Original ResearchDisease control rateProgression-free survivalDuration of responseCo-mutationsOverall survivalECOG PS 0-1Impact of co-mutationsInvestigate progression-free survivalEfficacy of sotorasibNon-sq NSCLCTP53 co-mutationsPD-L1 expressionPhase II studyAdverse event ratesTumor suppressor genePD-(L)1PD-L1Platinum chemotherapySystemic therapyCtDNA analysisII studyPrimary endpointGrade 3Resistance patternsControl rate
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
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