Phase Ib/II study of ceritinib in combination with ribociclib in patients with ALK-rearranged non-small cell lung cancer
Mené sur 27 patients atteints d'un cancer du poumon non à petites cellules présentant des réarrangements du gène ALK (âge médian : 57 ans), cet essai de phase IB/II évalue la dose maximale tolérée du céritinib en combinaison avec le ribociclib et l'efficacité, du point de vue du taux de réponse globale, de cette combinaison
Résumé en anglais
Background : Preclinical data show that the combination of an ALK inhibitor (ALKi) with a cyclin-dependentkinase 4/6 inhibitor (CDK4/6i) may act synergistically to overcome drug resistance mechanisms.Here, we assessed the safety, tolerability, and preliminary clinical activity of ceritinib,an ALKi in combination with ribociclib, a CDK4/6i, in patients with ALK–rearranged non–small cell lung cancer (NSCLC).
Methods : This was a multicenter, open-label, phase Ib/II dose-escalation study to determinethe maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) for ceritinib plus ribociclib therapy.
Results : Twenty-seven adult patients with ALK–rearranged advanced NSCLC with an ECOG PS ≤2 were enrolled into five cohorts to receivevarious dose combinations of ceritinib (range, 300–450 mg/day) and ribociclib (range, 100–300 mg/day). Median age of patients was 57 years. MTDs were not reached in this study.Enrollment into phase Ib was terminated early and phase II was not opened due to changesin the ALK-rearranged NSCLC treatment landscape. Ceritinib 300 mg/day and ribociclib 200 mg/day (3-weeks-on/1-week-off schedule) was identified as the RP2D. Among the27 evaluable patients, the overall response rate (ORR) was 37.0% (95% CI, 19.4–57.6)and median progression-free survival (mPFS) was 21.5 months (95% CI, 5.5–25.0). At RP2D, the ORR was 50.0%, disease control rate was 75%,and mPFS was 24.8 months (95% CI, 5.5–25.1). Safety profile of the combination therapywas consistent with single-agent safety data.
Conclusion : Combination of ceritinib and ribociclib showed clinical activity with a manageablesafety profile in patients with advanced ALK-rearranged NSCLC.
