CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer

Abstract

Epidermal growth factor receptor (EGFR) is overexpressed in many epithelial tumors and its role in the development of non-small-cell lung cancer (NSCLC) is widely documented. CIMAvax-EGF is a therapeutic cancer vaccine composed by recombinant EGF conjugated to a carrier protein and emulsified in Montanide ISA51. Vaccination induces antibodies against self-EGF that block EGF–EGFR interaction and inhibit EGFR phosphorylation. Five clinical trials were conducted to optimize vaccine formulation and schedule. Then, two randomized studies were completed in advanced NSCLC, where CIMAvax-EGF was administered after chemotherapy, as ‘switch maintenance’. The vaccine was very well tolerated and the most frequent adverse events consisted of grade 1/2 injection site reactions, fever, headache, vomiting and chills. CIMAvax was immunogenic and EGF concentration was reduced after vaccination. Subjects receiving a minimum of 4 vaccine doses had a significant survival advantage. NSCLC patients with high EGF concentration at baseline had the largest benefit, comparable with best maintenance therapies.

Keywords:

• cancer vaccine
• clinical trials
• epidermal growth factor
• epidermal growth factor receptor
• lung cancer
• non-small-cell lung cancer

Financial & competing interests disclosure

A Lage, C Rodríguez, B Garcia and T Crombet work for the Center of Molecular Immunology, which sponsored all the clinical studies and produces CIMAvax-EGF. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Epidermal growth factor receptor (EGFR) activation is associated with high proliferation, invasiveness, metastization and anti-apoptosis of tumor cells.

• EGF is one of the most important ligands of the EGFR.

• High EGF concentration is a worse prognostic factor for advanced lung cancer patients after frontline chemotherapy.

• CIMAvax-EGF is a therapeutic cancer vaccine aimed to generate neutralizing antibodies against EGF, which would block the union between EGF and EGFR.

• CIMAvax-EGF is very safe. Most frequent adverse events are grade 1 or 2 injection site reactions, chills, fever, nausea and vomiting.

• Patients receiving at least 4 doses of the vaccine had a significant advantage in overall survival.

• Patients with high EGF concentration in sera had the largest benefit, comparable with best ‘switch maintenance’ therapies.