ZN-c3 + encorafenib + cetuximab

ZN-c3 + encorafenib + cetuximab is an investigational **triplet combination therapy** under development for advanced solid tumors, most notably **metastatic colorectal cancer (mCRC)** with BRAF V600E mutations. - **ZN-c3** is an oral small-molecule inhibitor of WEE1 kinase, a regulator of the G2/M checkpoint in the cell cycle, developed by Zentalis Pharmaceuticals. Inhibition of WEE1 can induce DNA damage and cell death selectively in tumor cells with defective DNA repair. - **Encorafenib** is an oral small molecule that inhibits mutant BRAF kinase, primarily BRAF V600E, thereby blocking aberrant MAPK pathway signaling implicated in cancer cell proliferation[1][4][5][6]. - **Cetuximab** is a chimeric monoclonal antibody targeting the epidermal growth factor receptor (EGFR), inhibiting its function and downstream signaling pathways, leading to reduced tumor growth and survival[1][3][4][5][6]. The rationale for combining these agents is to co-target parallel signaling and DNA damage response pathways, aiming to overcome resistance mechanisms and achieve synergistic anticancer activity, particularly in BRAF V600E mutant mCRC, where dual targeting of BRAF and EGFR has proven efficacy and WEE1 inhibition is hypothesized to enhance DNA damage-induced cell death.

Other names

encorafenibcetuximab