Source: http://cccm-studienregister.de/trials/526?locale=de
Timestamp: 2017-10-22 20:48:15
Document Index: 246081962

Matched Legal Cases: ['art 1', 'art 2', 'art 1', 'art 1', 'art 2', 'art 2', 'art 2', 'art 1', 'art 2']

Studie CMEK162B2301 COLUMBUS
CMEK162B2301 COLUMBUS
The study is amended to consist of 2 parts, a modified study part 1 and a newly added study
part 2 that addresses a recent request from the US FDA to add an arm of 300mg QD LGX818
plus 45mg BID MEK162 and compare this arm against the LGX818 monotherapy arm.
To account for the evolving treatment landscape in BRAF mutant advanced melanoma with respect to the combination of targeted therapies, the testing strategy in study part 1 was modified to a hierarchical testing of PFS for: (i) LGX818 450mg QD plus MEK162 45mg
BID (denoted as Combo 450) vs. vemurafenib (primary endpoint), and (ii) Combo 450 vs.
LGX818 monotherapy (part 1 key secondary endpoint).
The analysis of LGX818 monotherapy vs. vemura-fenib was changed to a secondary endpoint. Due to new emerging data on targeted agents PFS assumptions were updated. These changes are supported by the recent results of two phase III studies (Combi-V and co-BRIM) that demonstrated an efficacy advantage of the combination of BRAF and MEK inhibitors (dabra-fenib plus trametinib and vemurafenib plus cobimetinib, respectively) over single agent vemurafenib (Larkin et al 2014; McArthur et al 2014; Robert et al 2014), and more mature data from a phase I/II study [CMEK162X2110] (LGX818 plus MEK162) and a phase I study [CLGX818X2101] (LGX818 monotherapy).
The newly added study part 2 will further define the contribution of MEK162 to the combination by assessing the same dose of LGX818 300mg QD in the combination arm than
in the monotherapy arm. This will provide further data to assess the contribution of MEK162 to the Combination and whether the contribution is by its own anti-tumor effect and/or by allowing delivery of a higher dose of the more active drug LGX818. Thus, in part 2, a new treatment arm consisting of LGX818 300mg QD plus MEK162 45mg BID (denoted as
Combo 300 arm) will be included and compared to LGX818 monotherapy at the same LGX818 dose (300mg QD). The testing of this part 2 key secondary endpoint will be hierarchically after the part 1 key secondary endpoint.
Overall survival (OS) for Combo 450 vs. vemurafenib will be presented as secondary
endpoint and tested hierarchically after the part 2 key secondary endpoint.
EudraCT-Nr.
2013-001176-38
KUM - Klinik und Poliklinik für Dermatologie und Allergologie, München
ICD-10-GM C43.9 Bösartiges Melanom der Haut, nicht näher bezeichnet
Ethikkommission - Bearbeitungsnummer
BfArM - Votum
BfArM - Bearbeitungsnummer
Approximately 900 adult patients (age ≥18), with histologically confirmed, locally advanced, unresectable or metastatic BRAF V600 mutant cutaneous melanoma or unknown primary melanoma (stage IIIB, IIIC or IV per American Joint Committee on Cancer [AJCC]) as determined by a Novartis designated central laboratory(ies), with no prior systemic anti-cancer therapy (treatment-naïve) or who have
progressed on or after prior first-line immunotherapy in the advanced or metastatic
setting, will be randomized in this study. Prior systemic treatment in the adjuvant
Hauptprüfer Carola Berking KUM - Klinik und Poliklinik für Dermatologie und Allergologie, München
Verantwortlicher Ansprechpartner Carola Berking KUM - Klinik und Poliklinik für Dermatologie und Allergologie, München