Racotumomab–alum vaccine for the treatment of non-small-cell lung cancer

Abstract

Racotumomab–alum vaccine is an anti-idiotypic vaccine able to mimic the tumor-associated antigen NeuGcGM3. Different Phase I clinical trials and compassionate use studies demonstrated its low toxicity and capacity to induce a strong anti-NeuGcGM3 response, able to bind and directly kill tumor cells expressing the antigen. A Phase II/III randomized double-blind clinical trial in advanced non-small cell lung cancer patients showed a significant improvement in overall survival and progression-free survival for racotumomab–alum versus placebo. Patients who developed anti-NeuGcGM3 antibodies capable of binding and killing NeuGcGM3 expressing tumor cells showed significantly longer median survival times. The impact of using racotumomab–alum as switch maintenance followed by second-line therapy is currently being explored in a new randomized, multinational Phase III study.

Keywords:

• anti-idiotypic antibody
• clinical trial
• NeuGcGM3
• NSCLC
• vaccine

Financial & competing interests disclosure

AM Vázquez is the inventor of patents related with racotumomab; however, she assigned her rights to the assignee Center of Molecular Immunology. 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

• Non-small-cell lung cancer (NSCLC) remains the most common cause of cancer-related death.

• NeuGc gangliosides are attractive targets for NSCLC immunotherapy since they are not naturally expressed in normal human tissues but were detected in NSCLC patients’ samples.

• The anti-Id vaccine racotumomab–alum is able to elicit a strong and specific antibody response against NeuGcGM3, able to recognize and directly kill tumor cells expressing the antigen.

• A Phase II/III randomized double-blind clinical trial with stage IIIb/IV NSCLC patients who have at least stable disease after first-line chemotherapy showed a significant increase in the OS and improved 2-year survival rates for the racotumomab–alum group in comparison with the placebo group.

• Among the vaccinated patients, significantly longer survival times were achieved by those who elicited IgM antibodies able to recognize at least 20% or kill at least 25% of NeuGcGM3-positive tumor cells.

• To confirm these results a randomized Phase III clinical trial in advanced NSCLC patients is ongoing, in which primary endpoint is OS.

Notes