SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR <i>BRAF</i> V600E-mutant mCRC
Elena Élez, Scott Kopetz, Josep Tabernero, Tanios Bekaii‐Saab, Julien Taı̈eb, Takayuki Yoshino, Gulam A. Manji, Kathrine C. Fernandez, Antonello Abbattista, Xiaosong Zhang, Van K. Morris
Abstract
Patients with both BRAF V600E mutations and microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) have poor prognosis. Currently, there are no specifically targeted first-line treatment options indicated for patients with mCRC whose tumors harbor both molecular aberrations. Pembrolizumab is a checkpoint inhibitor approved for the treatment of MSI-H/dMMR mCRC, and the BRAF inhibitor encorafenib, in combination with cetuximab, is approved for previously treated BRAF V600E-mutant mCRC. Combination of pembrolizumab with encorafenib and cetuximab may synergistically enhance antitumor activity in patients with BRAF V600E-mutant, MSI-H/dMMR mCRC. SEAMARK is a randomized phase II study comparing the efficacy of the combination of pembrolizumab with encorafenib and cetuximab versus pembrolizumab alone in patients with previously untreated BRAF V600E-mutant, MSI-H/dMMR mCRC.