PURPOSE:EGFR inhibition, combined with chemotherapy, forms a mainstay of treatment of first-line RAS wild-type (RASwt) metastatic CRC (mCRC). We compared the anti-EGFR antibody, A140, with cetuximab (both combined with chemotherapy) for RASwt mCRC.
METHODS:In this phase 3, randomized, double-blind, multi-center equivalence trial in China, patients were randomized (1:1) to oxaliplatin, 5-fluorouracil, and leucovorin (modified [m] FOLFOX6), plus either A140 or cetuximab for ≤ 16 weeks until disease progression or unacceptable toxicity. After the 16-week treatment period, patients who investigators deemed could benefit received A140 plus mFOLFOX6. Eligible patients were 18-75 years old with histologically confirmed RASwt mCRC and an Eastern Cooperative Oncology Group (ECOG) score of 0-1. Primary endpoint was objective response rate (ORR [RECIST v1.1]), per independent review committee, over the 16 weeks. A140 was considered equivalent if the 90 % CIs for the ORR ratio were between 0.83 and 1.20. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, immunogenicity, and pharmacokinetics.
RESULTS:Overall, 688 patients were randomized to A140 (n = 341) or cetuximab (n = 347). As of 22-Mar-2023, the ORR was 71.0 % (A140) and 77.5 % (cetuximab); the ORR ratio was 0.93 (90 % CI, 0.87-0.99). With a median follow-up of 19.6 months, no notable differences in PFS, OS, or duration of response were observed between arms. Safety profiles and immunogenicity were similar between arms and no new safety signals were observed.
CONCLUSION:A140 plus mFOLFOX6 is equivalent to cetuximab plus mFOLFOX6 for RASwt mCRC, with no appreciable differences in safety profiles. A140 plus mFOLFOX6 may provide a new treatment option for patients with RASwt mCRC.