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Pfizer has halted a Phase III trial of tremelimumab after it failed to show superiority over standard chemotherapy in advanced melanoma patients. The study represented the drug's most advanced stage of clinical development in oncology. Although Pfizer aims to continue developing tremelimumab in other oncology indications, its failure in melanoma represents a significant setback for the company.
Tremelimumab is a fully human anti-CTLA4 (cytotoxic T-lymphocyte antigen 4) IgG2 monoclonal antibody developed by Pfizer for its potential therapeutic application in melanoma, non-small cell lung cancer (NSCLC) and colorectal cancer. CTLA4 is a CD28-family receptor expressed mainly on T-lymphocyte that acts to inhibit T-lymphocyte function. The A3671009 Phase III trial in 630 advanced melanoma patients was investigating tremelimumab compared to standard chemotherapy, consisting of dacarbazine and Schering-Plough's Temodar (temozolomide). However, Pfizer discontinued this trial when interim data found that tremelimumab did not demonstrate superiority over standard chemotherapy.
Pfizer has already stated its intention to determine whether tremelimumab showed benefit in any of the advanced melanoma patients that took part in the trial. Analysis of the current Phase III trial may help identify certain patients that show a better response to tremelimumab and guide future development. Further study outcomes are expected to be announced at the American Society for Clinical Oncology Annual Meeting in June 2008.
Melanoma is the least common but most serious form of skin cancer affecting around 50,000 people annually in the US alone. The incidence of melanoma continues to increase as a result of higher exposure to ultraviolet (UV) light. Fortunately, many patients are diagnosed early with a localized stage due to increased awareness of the risks of UV exposure and symptoms of melanoma. However, in advanced-stage melanoma patients, chemotherapy or immunotherapy may be required in addition to surgery.
Dacarbazine is currently the only cytotoxic agent approved for use in advanced melanoma while Temodar lies in pre-registration. Immunotherapeutic agents approved for melanoma include Schering-Plough's Intron-A (interferon alpha-2b) and Chiron's Proleukin (aldesleukin). However, high toxicities and poor survival rates associated with current treatment highlight a major need for safer and more effective agents in advanced melanoma patients.
Despite the setback in melanoma, Pfizer hopes to continue clinical development of tremelimumab, which is currently in Phase II development for NSCLC and colorectal cancer. Tremelimumab will need to show superior efficacy and safety in additional indications to allow Pfizer to demonstrate the drug's full therapeutic potential in oncology.
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