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More Encouraging News - They will be even more excited about the combination resultshttps://www.onclive.com/peer-exchange/advanced-ovarian-cancer-strategies/novel-treatment-strategies-in-recurrent-ovarian-cancer I can’t believe that we are now talking about the fourth area of targeted therapy, antibody-drug conjugates. The leading candidate would be mirvetuximab soravtansine. Tell us about that. Kathleen Moore, MD: Mirvetuximab soravtansine is an antibody-drug conjugate. It’s an antibody that targets folate receptor alpha, which is highly overexpressed in epithelial ovarian cancer. We don’t really know why or what it’s doing there, but it’s there and there is relatively little to no expression on normal tissue. Conjugated to the antibody are molecules of a very potent cytotoxin called DM4, which is a microtubular toxin. These cytotoxins that are on these ADCs are active at the picomolar level. They’re really potent, but you are only getting a few molecules on each one. It’s intravenous. It’s given every 21 days. Patients have to be screened with archival tissue to make sure that they have moderate to high expression of folate receptor alpha. Bradley J. Monk, MD, FACS, FACOG: The target, yes. Kathleen Moore, MD: The phase I expansion was published in the Journal of Clinical Oncology. Patients with recurrent platinum-resistant ovarian cancer, who were relatively heavily pretreated, had an overall response rate of about 25%. That was good. But when we looked at that group of patients who had 1 to 3 prior lines of therapy, excluding the low expressors, the response rate was over 40%. And so, that drove the development of FORWARD I, which is the randomized phase III trial in that same population. Bradley J. Monk, MD, FACS, FACOG: This will be, again, the fourth category of active agents. When may we have this available in clinic? Kathleen Moore, MD: The readout of FORWARD I should happen in the first half of 2019. That’s pretty exciting. Then, the submission would go from there. There are other antibody-drug conjugates that are FDA-approved in other disease types—breast cancer and hematologic malignancies. There are a number of these in the pipeline for ovarian cancer, which has a lot of novel antigens. We don’t have a lot of mutations to target, but we have a lot of weird stuff on the surface. This may be a really fruitful line of research for our patients. |
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