...- Unresectable locally advanced or metastatic NSCLC with EGFR activating mutation (excluding exon 20 insertion) and presence of the T790M mutation...

...- Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B....

...• ORR and DR according to RECIST 1.1 as determined by investigatorreview, and OS• invPFS, ORR, DR, and OS in patients with baseline T790M mutationsconfirmed by central EGFR mutation assay•Change from baseline in QOL as measured using the PRO of EORTCQLQ-C30, EORTC QLQ-LC13, the DLQI, and the EQ-5D followingtreatment with CO-1686 versus erlotinib• Treatment-emergent AEs, laboratory abnormalities and ECGabnormalities• Plasma PK parameters for CO-1686 based on sparse sampling`- ORR and DR according to RECIST 1.1 as determined by investigator review, and OS- invPFS, ORR, DR, and OS in patients with baseline T790M mutations confirmed by central EGFR mutation assay- Change from baseline in QOL as measured using the PRO of EORTC QLQ-C30, EORTC QLQ-LC13, the DLQI, and the EQ-5D following treatment with CO-1686 versus erlotinib- Treatment-emergent AEs, laboratory abnormalities and ECG abnormalities- Plasma PK parameters for CO-1686 based on sparse sampling - TRO y DR según RECIST (versión 1.1) conforme lo determine el investigador mediante su evaluación y la ST- SSPinv, TRO, DR y ST en pacientes con mutaciones T790M en el momento inicial, confirmadas por ensayo central de mutación en el EGFR- Cambio desde el momento inicial en la CDV, valorado mediante los cuestionarios RSP de EORTC QLQ-C30, EORTC QLQ-LC13, el DLQI y el EQ-5D tras el tratamiento con CO-1686 en comparación con erlotinib- AAs durante el tratamiento, anomalías analíticas y electrocardiográficas (ECG)- Parámetros FC en plasma para CO-1686 a partir de muestreos puntuales`• ORR and DR according to RECIST 1.1 as determined by investigator review, and OS• invPFS, ORR, DR, and OS in patients with baseline T790M mutations confirmed by central EGFR mutation assay•Change from baseline in QOL as measured using the PRO of EORTC QLQ-C30, EORTC QLQ-LC13, the DLQI, and the EQ-5D following treatment with CO-1686 versus erlotinib• Treatment-emergent AEs, laboratory abnormalities and ECG abnormalities• Plasma PK parameters for CO-1686 based on sparse sampling • TRO et DR, et TCM selon les critères RECIST version 1.1, déterminés par l’évaluation de l’investigateur, et SG• SSPinv, TRO, DR, et SG chez des patients porteurs de mutations T790M, à la visite de référence, confirmées par un test de recherche des mutations EGFR réalisé centralement• Variations par rapport à la visite de référence de la QdV mesurée à l’aide des RRP du questionnaire EORTC QLQ C30, EORTC QLQ LC13, de l’index DLQI, et du questionnaire EQ-5D après traitement par le CO-1686 par rapport à l’ertolinib• Événements indésirables (EI) apparus pendant le traitement, anomalies biologiques et anomalies à l’électrocardiogramme (ECG) • Paramètres PK plasmatiques du CO-1686 sur des échantillons épars`• ORR and DR according to RECIST 1.1 as determined by investigator review, and OS• invPFS, ORR, DR, and OS in patients with baseline T790M mutations confirmed by central EGFR mutation assay• Change from baseline in QOL as measured using the PRO of EORTC QLQ-C30, EORTC QLQ-LC13, the DLQI, and the EQ-5D following treatment with CO-1686 versus erlotinib• Treatment-emergent AEs, laboratory abnormalities and ECG abnormalities• Plasma PK parameters for CO-1686 based on sparse sampling • ORR e DR secondo i criteri RECIST Versione 1.1, determinati dall’analisi dello sperimentatore, e OS• PFSsper, ORR, DR e OS nei pazienti con mutazioni T790M al basale confermate dal test delle mutazioni dell’EGFR eseguito a livello centrale• Variazione rispetto al basale della QOL, misurata utilizzando i PRO di EORTC QLQ C30, EORTC QLQ LC13, l’indice DLQI e il questionario EQ-5D in seguito al trattamento con CO-1686 rispetto a erlotinib• (EA emergenti dal trattamento, anomalie di laboratorio e anomalie nell’elettrocardiogramma (ECG) • Parametri PK plasmatici per CO-1686 basati su campionamento ridotto...

...- Documented evidence of T790M mutation in EGFR following disease progression on the first single agent EGFR TKI....

...T790M-positive patients treated with rociletinib in our study had a sustained clinical benefit. A response rate of 59% with prolonged disease control was noted. Although the best responses were observed among those with T790M-positive cancers, rociletinib showed some antitumor activity in patients without a documented T790M mutation.

...epidermal growth factor receptor (EGFR) kinase domain mutations are a common cause of non-small-cell lung cancer (NSCLC), a major subtype of lung cancers…The new-generation inhibitors such as AZD9291, HM61713, CO-1686 and WZ4002 can overcome T790M through covalent binding to Cys 797, but ultimately lose their efficacy upon the emergence of the C797S mutation...

We treated 9 EGFR-mutant patients with rociletinib and subsequent osimertinib... Seven had documented T790M-positive status prior to treatment with rociletinib, and 8 were T790M-positive prior to treatmentwith osimertinib. Rociletinib was discontinued for progressive disease (PD) in all.