Daphne Stewart1, Mihaela Cristea. 1. Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California, USA.
Abstract
PURPOSE OF REVIEW: Antibody drug conjugates (ADC) are a novel class of cancer therapeutics, delivering cytotoxic therapy directly to cancer cells, and show promise in the management of platinum-resistant ovarian cancer. Herein we summarize the ADC landscape currently in clinical study. RECENT FINDINGS: Mirvetuximab Soravtansine, IMGN853, is an ADC targeting the folate receptor alpha (FRα) and has demonstrated promising single agent activity and a favorable toxicity profile in FRα-positive, platinum-resistant, epithelial ovarian cancer (EOC). The antitumor effect is seen primarily in less heavily pretreated EOC patients with moderate-to-high FRα tumor expression. A phase III study, randomizing patients to either IMGN853 or the physician's choice of single-agent chemotherapy has completed accrual. Additional ADC are being evaluated in ovarian cancer including agents that target NaPiB2, Trop2, mesothelin, and MUC16 are in phase 1 clinical trials. SUMMARY: ADC bind antigens overexpressed on cancer cells and provide site-selective drug delivery, with the goal to increase therapeutic efficacy of cytotoxics while decreasing the off-target toxicity of the payloads. With appropriate antigen selection and adequate, measurable antigen threshold targets, these new agents may provide an improved strategy for overcoming resistance to standard chemotherapy in ovarian cancer.
PURPOSE OF REVIEW: Antibody drug conjugates (ADC) are a novel class of cancer therapeutics, delivering cytotoxic therapy directly to cancer cells, and show promise in the management of platinum-resistant ovarian cancer. Herein we summarize the ADC landscape currently in clinical study. RECENT FINDINGS:Mirvetuximab Soravtansine, IMGN853, is an ADC targeting the folate receptor alpha (FRα) and has demonstrated promising single agent activity and a favorable toxicity profile in FRα-positive, platinum-resistant, epithelial ovarian cancer (EOC). The antitumor effect is seen primarily in less heavily pretreated EOC patients with moderate-to-high FRα tumor expression. A phase III study, randomizing patients to either IMGN853 or the physician's choice of single-agent chemotherapy has completed accrual. Additional ADC are being evaluated in ovarian cancer including agents that target NaPiB2, Trop2, mesothelin, and MUC16 are in phase 1 clinical trials. SUMMARY: ADC bind antigens overexpressed on cancer cells and provide site-selective drug delivery, with the goal to increase therapeutic efficacy of cytotoxics while decreasing the off-target toxicity of the payloads. With appropriate antigen selection and adequate, measurable antigen threshold targets, these new agents may provide an improved strategy for overcoming resistance to standard chemotherapy in ovarian cancer.
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