Safety, immunogenicity and preliminary efficacy of multiple-site vaccination with an Epidermal Growth Factor (EGF) based cancer vaccine in advanced non small cell lung cancer (NSCLC) patients

Abstract

The prognosis of patients with advanced non small cell lung (NSCLC) cancer remains dismal. Epidermal Growth Factor Receptor is over-expressed in many epithelial derived tumors and its role in the development and progression of NSCLC is widely documented. CimaVax-EGF is a therapeutic cancer vaccine composed by human recombinant Epidermal Growth Factor (EGF) conjugated to a carrier protein, P64K from Neisseria Meningitides. The vaccine is intended to induce antibodies against self EGF that would block EGF-EGFR interaction. CimaVax-EGF has been evaluated so far in more than 1000 advanced NSCLC patients, as second line therapy. Two separate studies were compared to assess the impact of high dose vaccination at multiple anatomic sites in terms of immunogenicity, safety and preliminary efficacy in stage IIIb/IV NSCLC patients. In both clinical trials, patients started vaccination 1 month after finishing first line chemotherapy. Vaccination at 4 sites with 2.4 mg of EGF (high dose) was very safe. The most frequent adverse events were grade 1 or 2 injection site reactions, fever, headache and vomiting. Patients had a trend toward higher antibody response. The percent of very good responders significantly augmented and there was a faster decrease of circulating EGF. All vaccinated patients and those classified as good responders immunized with high dose at 4 sites, had a large tendency to improved survival.

Therapeutic cancer vaccine: phase I clinical tolerance study of Hu-rhEGF-rP64k/Mont in patients with newly diagnosed advanced non-small cell lung cancer

“…Successive cohorts were given doses of 1.2 mg (group B), 1.8 mg (group C), 2.4 mg (group D) the same dose intervals. The dose groups were determined on the basis of the vaccine’s safety information available from previous clinical studies [ 8 , 13 , 14 ]. Each vaccine dose was administered at 1 injection site, deltoid region (group A), 2 injection sites, deltoids regions (group B), 3 injection sites, deltoids regions and gluteus region (group C) and 4 injection sites, deltoids and gluteus regions (group D).…”

The Future of Immunotherapy in the Treatment of Lung Cancer

“…CimaVax, a recombinant EGFbased vaccine is designed to cause an antibody immune response to EGF, thereby depleting circulating EGF [42,43]. In a randomized Phase II trial, patients with stage IIIB or IV NSCLC were allocated to receive either CimaVax or BSC alone as a second-line treatment.…”

A New Statistical Approach for Quality of Life Questionnaires in the Assessment of Non-Small-Cell Lung Cancer Cuban Patients

“…and item #30: how would you rate your overall quality of life during the past week?) coded with a 7-point analogue scale that ranges from very poor (1) to excellent (7). The QLQ-LC13 has 12 questions assessing lung cancer associated symptoms and treatment related side effects.…”

“…Their current scoring and interpretation assume (i) a multi-dimensionality of the latent constructs that underlie the items measurement with major dimensions for functionality and symptoms severity, and (ii) a similar item discrimination within each dimension that is reflected by the unweighted approach to estimate the appropriate total score as reported in the EORTC manual [6]. We have tested these assumptions by analyzing the item responses and conducting confirmatory factor analysis (CFA) of both QoL scales in lung cancer patients participating in several trials with a therapeutic anticancer vaccine (Cimavax EGF) manufactured and licensed in Cuba for use in adult patients with stage IIIB/IV non-small-cell lung cancer (NSCLC), and designed to boost the individual's immune response against the epidermal growth factor (EGF) [7][8][9][10].…”