Compound Name:IpilimumabMolecular Target:CTLA-4 (cytotoxic T-lymphocyte-associated antigen)Molecular Structure:Chimeric IgG1?, recombinant monoclonal antibodyLicensed Indication:Melanoma that is metastatic or unresectableManufacturer and/or Distributor:Bristol-Myers SquibbInitial FDA Approval:2011Summary:Ipilimumab (Yervoy) is a fully human IgG1k monoclonal antibody that binds to the T-cell surface molecule CTLA-4 (cytotoxic T-lymphocyte-associated antigen) and blocks its interaction with its ligands, CD80 and CD86. This prevents the delivery of a negative signal to the T cells, and thus augments their activation and proliferation. This is thought to enhance an active immune response by T cells directed at cancer cells. Ipilimumab is administered as an intravenous infusion in 4 doses over 9 weeks. Ipilimumab was approved by the FDA on March 25, 2011 for the treatment of unresectable or metastatic melanoma. Additionally, ipilimumab is undergoing clinical trials for the treatment of non-small cell lung carcinoma (NSCLC), small cell lung cancer (SCLC) and metastatic hormone-refractory prostate cancer. On September 2015, the FDA granted accelerated approval to nivolumab in combination with ipilimumab for the treatment of patients with BRAF V600 wild-type, unresectable or metastatic melanoma. The approval of ipilimumab for treatment of melanoma was based on a trial of 676 previously-treated patients with unresectable or metastatic disease. Overall median survival improved from 6 months in the control group to 10 months in the ipilimumab groups. Interestingly, approximately 20% of the ipilimumab-treated patients have shown long-term survival (>3 years) in follow-up studies. Phase III study in 951 patients, EORTC 18071, has also indicated that adjuvant therapy with ipilimumab for patients with high-risk stage III melanoma decreases the relative risk of cancer recurrence by 25% compared to placebo. The T-cell activation and proliferation set off by ipilimumab can lead to the targeting of various organ systems by an immune-mediated attack that can be severe or even fatal. These adverse reactions include hepatitis, enterocolitis, dermatitis, neuropathy, and endocrinopathies, particularly of the thyroid. Management of immune-mediated adverse reactions includes permanent discontinuation of ipilimumab and initiation of high dose corticosteroids. Milder adverse reactions include fatigue, diarrhea, pruritus, rash and colitis.References

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