Cetuximab Biosimilar Receives NMPA Approval For RAS/BRAF Wild-Type CRC

China’s National Medical Products Administration (NMPA) has approved the cetuximab beta injection (Enlituo; formerly CMAB009) in combination with leucovorin, fluorouracil, and irinotecan (FOLFIRI) for marketing as a first-line treatment in RAS/BRAF wild-type metastatic colorectal cancer (mCRC), according to an announcement from Simcere Zaiming.¹

This cetuximab biosimilar is a recombinant EGFR monoclonal antibody independently developed in China that was designed to effectively avoid glycosylation modification leading to hypersensitivity in patients receiving the drug.

This regulatory decision, made on June 25, 2024, was supported by results from both a phase 2/3 study and a phase 3 confirmatory clinical trial. In the prospective phase 3 study, the addition of cetuximab beta to FOLFIRI significantly increased the median progression-free survival (PFS) to 13.133 months vs 9.567 months with FOLFIRI alone in patients with RAS/BRAF wild-type mCRC (n = 505; P = .004). Additionally, the combination produced an objective response rate (ORR) of 69.1% and a median overall survival (OS) of 2.322 years. The corresponding ORR and median OS with FOLFIRI was 42.3% (P < .001) and 1.900 years (P = .024).

The marketing application for cetuximab beta was previously accepted by the NMPA in March, 2023. On August 18, 2023, drug developer Simcere Pharmaceutical Group entered into a cooperation agreement with Mabpharm Limited and obtained the exclusive commercial rights to this drug in the Chinese mainland.

“It’s initial indication for colorectal cancer addresses a large patient population,” Dr Renhong Tang, chairman of Simcere Zaiming, emphasized in a news release. “The product synergizes well with Simcere Zaiming’s existing offerings, and efforts are underway to accelerate its commercialization, benefiting more [patients with] cancer.”

“This provides clinicians and patients with updated therapeutic options. By collaborating with Simcere Zaiming’s Marketing Team, we are able to rapidly realize the clinical value of Enlituo, benefiting hundreds of thousands of patients in China with an effective and affordable biological new drug,” Dr Hao Wang, chief executive officer of Mabpharm, added.

The open-label, randomized, controlled, multicenter, prospective phase 3 study is enrolling patients between 18 and 75 years of age with histologically confirmed adenocarcinoma of the colon or rectum that is RAS/BRAF wild-type. Patients are also required to have 1 or more measurable lesions by CT or magnetic resonance imaging according to RECIST v1.1; an ECOG performance status of 0 or 1 at trial entry; and a life expectancy of at least 3 months. Prior radiotherapy or surgery in the 30 days before trial treatment and inadequate hepatic, marrow, renal, or liver function will exclude patients from the study.²

Upon enrollment, patients are randomly assigned to receive the combination or chemotherapy alone. In addition to the FOLFIRI regimen, patients in the combination arm will also receive cetuximab beta at an initial dose of 400 mg/m2 and subsequent 250 mg/m2 doses every 7 days. Treatment will continue until disease progression, withdrawal of consent, or unacceptable toxicity.

The study’s primary end point is PFS per RECIST v1.1. Key secondary end points include best ORR, OS, duration of response, and quality of life assessment.

References

1. Simcere Zaiming announce approval of cetuximab beta in China by the NMPA. News release. Simcere Zaiming. June 26, 2024. Accessed June 26, 2024. https://www.simcere.com/en/news/detail.aspx?mtt=459#:~:text=On%20June%2025%2C%202024%2C%20Simcere,in%20collaboration%20with%20Mabpharm%20Limited%20(
2. CMAB009 combined with FOLFIRI first-line treatment in patients with RAS/​BRAF wild-type, metastatic colorectal cancer. ClinicalTrials.gov. Updated April 10, 2024. Accessed June 26, 2024. https://clinicaltrials.gov/study/NCT03206151

could NOT find this NCT