Cetuximab every second week in combination with daily encorafenib in patients with BRAF V600E mutated metastatic colorectal cancer: Interim analysis from NEW BEACON.

Abstract

153 Background: Weekly administered cetuximab in combination with the BRAF inhibitor encorafenib has improved survival in pre-treated patients (pts) with BRAF V600E mutated (BRAFmut) metastatic colorectal cancer (mCRC), with a median progression free survival (PFS) of 4.3 months in the BEACON study. It is now standard-of-care in the second line treatment. However, a regimen with cetuximab administered every second week may demonstrate comparable efficacy and is more convenient for the pts. Thus, we initiated the NEW BEACON study investigating cetuximab given every second week together with daily encorafenib. Details on the rationale and aims of the study have previously been published (doi: 10.1186/s12885-022-10420-x.). Methods: NEW BEACON is an open-label, single-arm, multicenter, phase II study including pts with pre-treated BRAFmut mCRC. The primary end point is 2 months PFS rate. We report here the result of a pre-specified interim analysis after treatment of the first 19 included pts. We collected fresh tumor tissues for comprehensive molecular profiling in order to explore features associated with response and resistance. Baseline genomic variants will be reported. Results: From February 2021 to February 2024 20 pts were included in the study. 1 patient never started study treatment due to rapid disease progression. At the data cut-off date 19 pts had initiated study treatment. The 2 months PFS rate was 89% (17/19 pts). We had tumor tissue for molecular profiling available from 12 pts. Pathogenic variants in TP53 were the most frequently detected co-mutations at baseline in 83% of pts (10/12 pts). Available preliminary safety, efficacy, and survival data and more extensive genomic data will be presented at the meeting. Conclusions: The preliminary PFS data from pts with BRAFmut mCRC treated with cetuximab every second week together with daily encorafenib is promising demonstrating a 2 months PFS rate of 89%. This is similar to what was reported from the BEACON study (2 months PFS rate of 84%). Loss-of-function mutations in tumor suppressor genes were frequently detected as co-mutations at baseline. Clinical trial information: EudraCT: 2020-003283-10 .