A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer
Planchard D, Wolf J, Solomon B, Sebastian M, Wermke M, Heist R, Sun J, Min Kim T, Reguart N, Sanmamed M, Felip E, Garrido P, Santoro A, Bootle D, Couillebault X, Gaur A, Mueller C, Poggio T, Yang J, Moschetta M, Dooms C. A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer. Lung Cancer 2024, 197: 107964. PMID: 39383771, DOI: 10.1016/j.lungcan.2024.107964.Peer-Reviewed Original ResearchNon-small cell lung cancerCell lung cancerBRAF-mutated non-small cell lung cancerLung cancerDose-escalation/dose-expansion studyTreatment-related adverse eventsAntitumor activityDose-limiting toxicityNRAS-mutant melanomaMEK1/2 inhibitor trametinibPartial responseInhibitor trametinibFrequent gradeSafety profileAdverse eventsPharmacodynamic effectsTrametinibGenetic alterationsMedian reductionPan-RAFIncreased lipasePatientsSecondary objectivesMRNA levelsEvaluate toleranceKROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC.
Gregorc V, González-Cao M, Salvagni S, Koumarianou A, Gil-Bazo I, Maio M, Viteri S, Majem M, Gutiérrez V, Bernabe Caro R, Sanmamed M, Zhu H, Shen H, Wang Y, Rosell R. KROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC. Journal Of Clinical Oncology 2024, 42: lba8511-lba8511. DOI: 10.1200/jco.2024.42.17_suppl.lba8511.Peer-Reviewed Original ResearchTreatment-related adverse eventsDisease control ratePhase II studyEpidermal growth factor receptorKRAS G12C inhibitorsDose reduction/interruptionBrain metastasesII studySafety profileG12C inhibitorsBaseline PD-L1 expressionBaseline brain metastasesActivation of epidermal growth factor receptorPD-L1 expressionTreating NSCLC patientsAnti-EGFR antibodiesFront-line treatmentKRAS G12C mutationGrowth factor receptorNSCLC ptsNSCLC modelsTumor shrinkageFrontline therapyNSCLC patientsOpen-labelPhase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure
Spreafico A, Couselo E, Irmisch A, Bessa J, Au-Yeung G, Bechter O, Svane I, Sanmamed M, Gambardella V, McKean M, Callahan M, Dummer R, Klein C, Umaña P, Justies N, Heil F, Fahrni L, Opolka-Hoffmann E, Waldhauer I, Bleul C, Staack R, Karanikas V, Fowler S. Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure. Frontiers In Oncology 2024, 14: 1346502. PMID: 38577337, PMCID: PMC10991832, DOI: 10.3389/fonc.2024.1346502.Peer-Reviewed Original ResearchTreatment-related adverse eventsAnti-drug antibodiesCytokine release syndromeFirst-in-humanT-cell engagersCheckpoint inhibitorsMetastatic melanomaT cellsDrug exposureDevelopment of anti-drug antibodiesActive drugImmune responseFirst-in-human studyDrug activity in vitroDose-escalation studyDose-escalation trialTumor necrosis factor-alphaB cell interactionsImpact of immune responsesActive drug exposureNecrosis factor-alphaAnti-tumor activityLoss of efficacyAssociated with developmentDose escalation