1259MO - Encorafenib plus binimetinib in patients (pts) with previously untreated BRAF V600E-mutant advanced non-small cell lung cancer (NSCLC): An open-label, multicenter phase II trial (IFCT-1904 ENCO-BRAF)

Background

Activating BRAF-V600 mutations are oncogenic drivers in NSCLC. Current ESMO guidelines recommend dabrafenib plus trametinib as preferred first-line treatment options or as subsequent treatment for BRAFV600E-mutant advanced NSCLC. The combination of BRAF inhibitor encorafenib plus MEK inhibitor binimetinib has demonstrated clinical efficacy in patients with BRAFV600E-mutant NSCLC and melanoma.

Methods

In this ongoing, open-label, single-arm phase 2 study (IFCT-1904), BRAFV600E-mutant NSCLC pts received encorafenib 450mg once daily plus binimetinib 45mg twice daily. Cohort A enrolled previously untreated pts (presented in this abstract) and cohort B pretreated pts. The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety.

Results

Cohort A enrolled 64 pts from 24 centres in France between Mar 2021 and Sept 2023. Median age was 70.7 years; 47% were males; 17.2% had baseline brain metastases and 35.9% were never-smokers. Median follow-up in the study was 18 months. Median duration of treatment was 8.8 months with encorafenib and 8.9 months with binimetinib. Investigator-assessed ORR was 66.7% (95% IC: 55.0% - 78.3%). Median DOR was 13 months (95% IC: 9.1-NR) and DCR was 85.7% (95% IC: 77.1% - 94.4%). Median PFS was 11.1 months (95% IC: 7.1-16.7) and median OS was not reached (95% IC: 20.7-NR). The most frequent treatment-related adverse events (TRAEs) were fatigue (42.2%), nausea (32.8%) and diarrhea (31.3%). The percentage of pts with at least one dose reduction was 34.4% for encorafenib and 32.8% for binimetinib (of which 90% for AE). Permanent discontinuation of encorafenib plus binimetinib due to TRAE occurred in 6/38 (15.8%) pts. Grade 3 TRAE retinal detachment was observed in 3 pts (4.7%).

Conclusions

In this phase 2 trial with treatment-naïve BRAFV600E-mutant advanced NSCLC, encorafenib plus binimetinib demonstrated robust clinical activity. The safety profile was manageable and consistent with previous studies in lung cancer and melanoma.

Clinical trial identification

EudraCT 2019-004621-24, NCT04526782.

Editorial acknowledgement

Legal entity responsible for the study

IFCT.

Funding

Pierre Fabre France + IFCT.

Disclosure

D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. J. Mazieres: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Pfizer, Jiangsu Hengruii, Blueprint, Daiichi Sankyo, Novartis, Amgen; Financial Interests, Institutional, Other: Roche, AstraZeneca, Pierre Fabre, BMS, Illumina. C. Mascaux: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Bristol Myers Squibb, Pfizer, MSD, Amgen; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche, Bristol Myers Squibb, Pfizer, Kephren, Janssens, Takeda, Sanofi, Novartis. F. Guisier: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Janssen, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Pfizer, Roche, Takeda. P. Tomasini: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Lilly, Janssen, Amgen, Takeda; Financial Interests, Institutional, Local PI: Roche, AstraZeneca, Amgen, Lilly, Takeda; Financial Interests, Institutional, Coordinating PI: Janssen. M. Wislez: Financial Interests, Personal, Speaker’s Bureau: Amgen, Bristol Myers Squibb, F. Hoffman La Roche, Janssen, MSD Oncology, AstraZeneca, Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Janssen, MSD Oncology, Sanofi; Non-Financial Interests, Personal, Advisory Board: F. Hoffman La Roche; Financial Interests, Personal, Other: F. Hoffman La Roche, Janssen; Non-Financial Interests, Institutional, Principal Investigator: MSD Oncology, Amgen, AstraZeneca, Bristol Myers Squibb, F. Hoffman La Roche, Janssen, Novartis, Merus, BeiGene, Dizal, AbbVie, Boehringer Ingelheim, Lilly, Verastem. D. Moro-Sibilot: Financial Interests, Personal, Advisory Board: Novartis, Roche, Pierre Fabre. S. Cousin: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Lilly, Roche; Non-Financial Interests, Principal Investigator: AstraZeneca, Daichi, Gilead, Takeda, Sanofi, MSD, GSK, BMS. A.B. Cortot: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, AstraZeneca, MSD, Pfizer, Novartis, Takeda, Roche; Financial Interests, Personal, Advisory Board: Novartis, Roche, Pfizer, Janssen, Exeliom, Amgen; Financial Interests, Institutional, Research Grant: Merck, Roche, AbbVie, Exeliom; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Local PI: Janssen, Roche, Sparta, Amgen, Mirati, AbbVie; Non-Financial Interests, Member of Board of Directors: French Thoracic Intergroup. S. Couraud: Financial Interests, Institutional, Funding: Adene, BD Bioscience, Cellgene, Chugai, Janssen, Lilly, Takeda, Transdiag, Volition; Financial Interests, Personal and Institutional, Funding: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis, Pfizer, Roche, Sanofi; Financial Interests, Personal, Funding: Health Event, Maat Pharma, Pierre Fabre; Non-Financial Interests, Leadership Role: National guidelines in thoracic oncology (ARISTOT); Non-Financial Interests, Member of Board of Directors: Société de Pneumologie de Langue Française, Adene. V. Fallet: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, F. Hoffman La Roche, Jansen, MSD Oncology, Novartis, Pfizer, Sanofi, Takeda. A. Madroszyk Flandin: Financial Interests, Personal, Advisory Board, board 24/05/23: Janssen; Financial Interests, Personal, Advisory Board, 10/2021: AstraZeneca. M. Pérol: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Eisai, Ipsen, AstraZeneca, AbbVie, AnHeart Therapeutics, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Medscape; Financial Interests, Personal, Advisory Board, Advisory board: Novocure; Financial Interests, Institutional, Research Grant: AstraZeneca, ROCHE, Takeda, Boehringer Ingelheim; Financial Interests, Personal, Steering Committee Member: Roche, Sophiagenetics, PharmaMar, AnHeart Therapeutics; Financial Interests, Personal, Other, DMSB: Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Amgen, Roche, AbbVie, Apollomics, AnHeart Therapeutics, Innate Pharma, Boehringer Ingelheim, Arrivent Biopharma, Daiichi Sankyo, Bayer; Financial Interests, Steering Committee Member: Lilly. C. Ricordel: Financial Interests, Personal, Advisory Board: Roche, Takeda, MSD, BMS, Janssen, Sanofi, AstraZeneca. All other authors have declared no conflicts of interest.