A phase II study of encorafenib and cetuximab (EC) beyond progression in combination with FOLFIRI in <i>BRAF</i> V600E-mutated metastatic colorectal cancer (mCRC).
Abstract
TPS3642 Background: BRAF V600E mutation occurs in approximately 10% of metastatic colorectal cancers (mCRC) and confers poor prognosis. While the combination of encorafenib and cetuximab (EC) has demonstrated improved outcomes in previously treated BRAF V600E-mutated mCRC patients (pts), the duration of response remains suboptimal with median progression-free survival (mPFS) of 4.3 months (m). Approximately half of pts (45%) receive subsequent treatment after EC progression, predominantly with chemotherapy (ChT). Data from the safety lead-in (SLI) of the BREAKWATER trial, assessing EC in combination with ChT doublet in the first-line setting, demonstrated manageable safety profile and promising early efficacy signals for EC in combination with FOLFIRI, despite pharmacokinetic interaction. Methods: ECLYPse (NCT06640166; EU CT Number 2023-508615-24-00) is a multicenter, single-arm, phase II study evaluating EC continuation beyond progression in combination with FOLFIRI in pts with BRAF V600E-mutated mCRC who progressed on second-line EC. Key eligibility criteria include: histologically confirmed colorectal adenocarcinoma, BRAF V600E mutation, documented disease progression on EC in second-line setting, benefit to previous treatment with EC (best response: complete response, partial response or stable disease lasting for at least 3 months), measurable disease according to RECIST 1.1 criteria, ECOG PS ≤1, and availability of archival tumor tissue. Patients receive encorafenib 300 mg daily, cetuximab 500mg/m2 iv every 2 weeks, and standard FOLFIRI regimen. The primary endpoint is 6-month PFS rate. Secondary endpoints include PFS, overall survival, duration of response, objective response rate, disease control rate, and safety. Translational analyses include comprehensive genomic profiling on archival tissue and serial ctDNA analysis. Tumor assessment with contrast-enhanced CT scan of thorax, abdomen and pelvis is performed every 8 weeks. Using a single-stage design with one-sided α = 0.05 and 80% power, 25 patients will be enrolled to detect an improvement in 6-month PFS rate from 10% (null hypothesis) to 30% (alternative hypothesis). If at least 7 pts will be alive and not progressing at 6 months, the treatment will be considered sufficiently active to warrant further investigation. The study is currently enrolling at multiple sites in Italy. Clinical trial information: NCT06640166 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Maria Alessandra Calegari
Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Lisa Salvatore
Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario, Agostino Gemelli, IRCCS, Roma, Italy
Michele Basso
Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Maria Laura Iaia
Medical Oncology and Palliative Care Department, Azienda Ospedaliera Cardinale G. Panico, Tricase (Lecce), Italy
Giulia Caira
Medical Oncology, Università Cattolica del Sacro Cuore and Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Alexia Spring
Medical Oncology, Università Cattolica del Sacro Cuore and Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Giovanni Trovato
Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli–IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
Luciana Giannone
Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Martina Ventola
Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Antonia Cosmai
Medical Oncology, Università Cattolica del Sacro Cuore and Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Linda Di Francesco
Medical Oncology, Università Cattolica del Sacro Cuore; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Maria Bensi
Medical Oncology, Università Cattolica del Sacro Cuore and Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Laura Chiofalo
Medical Oncology, Università Cattolica del Sacro Cuore and Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Paola Troisi
Medical Oncology, Università Cattolica del Sacro Cuore and Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
Anna Ceccarelli
Medical Oncology, Università Cattolica del Sacro Cuore and Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Giustina Valente
Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Carmelo Pozzo
Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
Alessandra Anna Anna Prete
Oncology Unit 1, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy
Federica Morano
Giampaolo Tortora