A140 Plus mFOLFOX6 Demonstrates Potential Among Patients With RAS Wild-Type Metastatic Colorectal Cancer

According to results from a phase 3 trial, A140, an anti-EGFR antibody, plus mFOLFOX6 demonstrated encouraging efficacy and safety compared to cetuximab plus mFOLFOX6 among patients with RAS wild-type metastatic colorectal cancer (mCRC). 

“EGFR inhibition, combined with chemotherapy, forms a mainstay of treatment of first-line RAS wild-type mCRC,” stated Rongrui Liu, Chinese PLA General Hospital, Beijing, China, and coauthors. “We compared the anti-EGFR antibody, A140, with cetuximab (both combined with chemotherapy) for [RAS wild-type] mCRC.” 

In this multicenter, double-blind trial, 688 patients were randomized on a 1-to-1 basis to receive either A140 (n = 341) or cetuximab (n = 347) plus mFOLFOX6 for ≤ 16 weeks or until disease progression or unacceptable toxicity. At 16 weeks, patients who could derive benefit received A140 plus mFOLFOX6. The primary end point was objective response rate (ORR). Key secondary end points included progression-free survival (PFS), overall survival (OS), duration of response, safety, and immunogenicity. 

At analysis, the ORR was 71% in the A140 arm and 77.5% in the cetuximab arm (hazard ratio [HR] 0.93; 90% confidence interval [CI], 0.87 to 0.99). No difference in PFS, OS, or duration of response was observed. The safety and immunogenicity profiles were similar between treatment arms. No new safety signals were identified.

“A140 plus mFOLFOX6 is equivalent to cetuximab plus mFOLFOX6 for [RAS wild-type] mCRC, with no appreciable differences in safety profiles,” concluded Dr Liu et al. “A140 plus mFOLFOX6 may provide a new treatment option for patients with [RAS wild-type] mCRC.”

Source: 

Liu R, Yin X, Bai Y, et al. A140 plus mFOLFOX6 compared with cetuximab plus mFOLFOX6 for first-line RAS wild-type metastatic colorectal cancer: A randomized clinical trial. Eur J Cancer. Published online: June 6, 2025. doi: 10.1016/j.ejca.2025.115566