A Randomized, Multicenter, Placebo-Controlled Clinical Trial of Racotumomab-Alum Vaccine as Switch Maintenance Therapy in Advanced Non–Small Cell Lung Cancer Patients

Abstract

Purpose: Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. This clinical trial was conducted to provide a preliminary estimate of efficacy and safety of racotumomab as switch maintenance for patients with advanced non-small cell lung cancer (NSCLC).Experimental design: Patients with stage IIIb/IV NSCLC who have at least stable disease after first-line chemotherapy were randomized 1:1 to racotumomab-alum (5 immunizations every 2 weeks and reimmunizations every 4 weeks) or placebo. Treatment was administered beyond progressive disease, until severe performance status worsening or toxicity. At progression, only five patients per group received further anticancer therapy. The primary endpoint was overall survival (OS).Results: One-hundred and seventy-six patients were randomized to racotumomab-alum (n ¼ 87) and placebo (n ¼ 89). Median OS was 8.23 and 6.80 months, respectively [HR, 0.63; 95% confidence interval (CI), 0.46-0.87; P ¼ 0.004]. Median progression-free survival (PFS) in vaccinated patients was 5.33 versus 3.90 months for placebo (HR, 0.73; 95% CI 0.53-0.99; P ¼ 0.039). The most common adverse events in the racotumomab-alum arm were burning and pain at the injection site, bone pain, and asthenia. A high antibody response of IgM and IgG isotype against the NeuGcGM3 ganglioside was obtained. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 cell line. Patients who developed anti-NeuGcGM3 antibodies capable to bind and kill 30% L1210 cells showed longer median survival times.Conclusions: Switch maintenance with racotumomab-alum is an effective and a well-tolerated treatment option for patients with advanced NSCLC. Clin Cancer Res; 20(14); 3660-71. Ó2014 AACR.

Structural Mimicry of the Dengue Virus Envelope Glycoprotein Revealed by the Crystallographic Study of an Idiotype–Anti-idiotype Fab Complex

“…3 in reference 3), and several of these antibodies were not derived from the same D1.3 clone. More recently, efforts to develop "idiotypic vaccines" for cancer treatment have been reported (15,16). Racotumomab, an antiidiotypic antibody targeting the NeuGcGM3 tumor-associated ganglioside, was developed, and a clinical trial was conducted to provide a preliminary estimate of the efficacy and safety of racotumomab in patients with advanced non-small-cell lung cancer (15).…”

“…More recently, efforts to develop "idiotypic vaccines" for cancer treatment have been reported (15,16). Racotumomab, an antiidiotypic antibody targeting the NeuGcGM3 tumor-associated ganglioside, was developed, and a clinical trial was conducted to provide a preliminary estimate of the efficacy and safety of racotumomab in patients with advanced non-small-cell lung cancer (15). In a separate study, the GD2 antigen, which is highly expressed on neuroblastoma cells in cases of pediatric malignancy with poor prognoses, was targeted through the use of a new human-mouse chimeric anti-idiotypic antibody named ganglidiximab: this antibody was successfully used as a protein vaccine in vivo to induce a GD2-specific humoral immune response (16).…”

Cytolytic tests with hyperimmune patient sera is a good prognostic tool in racotumomab immunotherapy in advanced non-small cell lung cancer

“…They termed this process as oncotic necrosis [17] . Neugcgm3 ganglioside-based vaccines have been tested in several Phase II-III studies in nonsmall cell lung cancer and melanoma [18][19][20][21] . racotumomab is currently registered in Cuba and Argentina in nonsmall cell lung cancer as a second line treatment after first line chemotherapy.…”

Antibodies to watch in 2015

“…Results of a preliminary study of racotumomab as switch maintenance for patients with advanced NSCLC were recently published. 17 The efficacy and safety of active specific immunotherapy with racotumomab with best supportive care compared to best supportive care in patients with advanced NSCLC who have achieved an objective response (partial or complete response) or stable disease with standard first-line treatment are being evaluated in a Phase 3 study (NCT01460472). The primary outcome measures is overall survival from treatment administration until date of death or last censored observation, on average up to 17 months, and the study completion date is September 2015.…”