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Background Gangliosides, especially NeuGc-GM3, are an attractive target for cancer immunotherapy. They do not express in normal human cells but are overexpressed in several solid tumors including NSCLC and are involved in tumor development and growth. Racotumomab is therapeutic vaccine which induces a cellular and humoral immune response against NeuGc-GM3 expressed in tumors. Phase I and II trials in melanoma, breast and lung cancer have shown the low toxicity and high immunogenicity of racotumomab. Methods Multicenter, randomized, placebo controlled, double blind clinical trial in patients with advanced (IIIB and IV) NSCLC who had an ECOG status ≤ 2 and had achieved partial or complete response or disease stabilization after completion of onco-specific treatment. 176 patients were randomized 1:1 to placebo or racotumomab. Initially 1 dose was administered every 14 days (induction period, 5 doses in total), followed by 1 dose every 28 days (maintenance period) until patient refusal or worsening of ECOG status. Results Safety: The most common adverse events were expected mild reactions at the injection site (pain and itching). No differences were observed between both groups. Overall Survival (OS): Intent to Treat Analysis (ITT): Survival since inclusion was 15.7 months (mean) and 8.3 months (median) in the racotumomab arm and 10.6 months (mean) and 6.3 months (median) in the placebo arm (log rank test, p= 0.02). OS rate (%) at 12 and 24 months was 38 % and 17 % in the racotumomab arm and 24 % and 7 % in the placebo arm. Per Protocol Population Analysis (PPP): Includes patients who received ≥ 5 doses of racotumomab/ placebo (135/174 patients, 77% of the patient population). Survival since inclusion was 18.9 months (mean) and 10.9 (median) in the racotumomab arm and 11.4 months (mean) and 6.9 months (median) in the placebo arm (log rank test, p= 0.002). OS rate (%) at 12 and 24 months: 48 % and 22 % in the racotumomab arm and 28 % and 8 % in the lacebo arm. Conclusions Immunization with racotumomab is safe. There is an OS benefit for racotumomab, both in the ITT and PPP analyses. Survival benefit appears to be increased when the patient's clinical condition allows completion of the induction period of vaccination. Disclosure R.E. Gomez: Is a full time employee at Elea Laboratories. M.L. Ardigo: Is a full time employee at Elea Laboratories. All other authors have declared no conflicts of interest. |
