2435 - A Single Arm, Open Label, Phase II, Multicenter Study to Assess the Detection of the BRAF V600 Mutation on cfDNA from Plasma in Patients with Advanced Melanoma

Background

BRAF V600 mutations occur in 40-50% of metastatic melanomas as the most common "oncogenetic driver" event. Currently, BRAF V600 mutation status is assessed on tumor tissue to identify patients eligible for treatment with a BRAF+/-MEK inhibitor. The goal of this study is to estimate the frequency of the BRAF V600 mutation in a new tumor tissue analysis triggered by a mutant plasma test result, for patients with BRAF wild-type status based on a prior tissue test.

Methods

This is a single arm, multicenter, open label, non-randomized Phase II clinical study in adult patients with unresectable/metastatic melanoma. Patients were tested for the presence of BRAF V600 mutation using the IdyllaTM diagnostic platform on plasma cfDNA. In patients with a prior tissue BRAF V600 wild-type result, a mutant BRAF V600 plasma result triggered a new tissue analysis. The study had a power of 90% to reject the null hypothesis of a 3% probability of identifying the BRAFV600 mutation in case the real probability is 10%.

Results

172 patients with known tissue test results were included (9.3% unresectable Stage IIIc and 90.7% Stage IV). The median time since diagnosis of metastatic melanoma was 19.3 (range: 0–268)) months. In 7 out of 118 patients (5.9%), previously determined as wild type BRAF V600 based on a tumor tissue test, a BRAF V600 mutation was found upon plasma cfDNA testing. In 5 of these 7 patients, presence of a BRAF V600 mutation could be confirmed in the tissue re-test. For 4.2% (5/118) the mutation could be shown in a re-test triggered by the mutant plasma cfDNA result. The one-sided test comparing this frequency with the a priori hypothesis of 3% was not significant (p = 0.215).

Conclusions

In 4.2% of the patients a known BRAF V600 wild-type status could be converted in a positive mutant status by retesting tumor tissue triggered by detection of a BRAF V600 mutation in cfDNA. Some patients could therefore benefit from plasma testing at the time of therapeutic decision making, although their number was not significantly more than the a priori required 3%. Identifying a BRAFwt subpopulation with the highest chance of having a BRAF V600mut cfDNA test result at the time of treatment decision making deserves further study.

Clinical trial identification

NCT02768207.

Editorial acknowledgement

Legal entity responsible for the study

Roche.

Funding

Roche.

Disclosure

P. Rutkowski: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Advisory / Consultancy: Blueprint Medicines; Speaker Bureau / Expert testimony: Eli Lilly. B. Jacobs: Full / Part-time employment: Biocartis. G.G. Maertens: Full / Part-time employment: Biocartis. V. Gadeyne: Full / Part-time employment: Roche. S. Liebert: Full / Part-time employment: Roche. B. Neyns: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (institution): Merck Srono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (institution): Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. All other authors have declared no conflicts of interest.