CLO19-036: Folate Receptor alpha Expression in Metastatic Triple-Negative Breast Cancer (TNBC)

Background: Folate receptor alpha (FRα) is a glycosyl phosphatidylinositol (GPI)-anchored cell surface protein that binds and internalizes folate, which is a cofactor required for DNA/RNA synthesis and cell growth and proliferation. There is a marked up-regulation of FRα in many solid tumors; in contrast, FRα has a minimal expression in adult normal tissue. Mirvetuximab soravtansine is an antibody drug conjugate (ADC) consisting of a maytansinoid, N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4), conjugated to an anti-FRα antibody, M9346A. Once bound to the FRα and internalized, the anti-mitotic agents are released and inhibit tubulin polymerization and microtubule assembly, leading to cell death. Here we report the expression of FRα+ on residual tumor samples in metastatic TNBC. Methods: 68 patients (Pts) with stage IV TNBC underwent prescreening to determine if residual tumor tissue expressed FRα. Formalin fixed paraffin embedded (FFPE) samples were sent to Ventana Translational Diagnostics CAP/CLIA Laboratory for analysis using an in-house developed assay, Ventana OptiView DAB Detection kit, and the Ventana BenchMark Ultra automated slide stainer. FRα expression was evaluated by board certified pathologists using a scoring scale 1+ (low), 2+ (medium), and 3+ (high). For the purposes of study entry, FRα expression on cell surface was required to be low, defined as >25% of cells having 1+ expression. Results: 12% (8/68) of evaluated TNBCs had moderate to high rates of FRα expression. The median age of pts screened for FRα was 53 years. Moderate to high FRα expression rates were more common in Black and Asian patients (Table 1). Conclusion: Our prospective study has demonstrated that moderate to high expression of FRα in metastatic TNBC is 12%, which is lower than previously reported. An ongoing phase II study will determine efficacy for mirvetuximab soravtansine in advanced TNBC. Acknowledgement: This study was approved and funded in part by the NCCN Oncology Research Program from general research support provided by ImmunoGen, Inc.

Abstract

Background: Folate receptor alpha (FRα) is a glycosyl phosphatidylinositol (GPI)-anchored cell surface protein that binds and internalizes folate, which is a cofactor required for DNA/RNA synthesis and cell growth and proliferation. There is a marked up-regulation of FRα in many solid tumors; in contrast, FRα has a minimal expression in adult normal tissue. Mirvetuximab soravtansine is an antibody drug conjugate (ADC) consisting of a maytansinoid, N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4), conjugated to an anti-FRα antibody, M9346A. Once bound to the FRα and internalized, the anti-mitotic agents are released and inhibit tubulin polymerization and microtubule assembly, leading to cell death. Here we report the expression of FRα+ on residual tumor samples in metastatic TNBC. Methods: 68 patients (Pts) with stage IV TNBC underwent prescreening to determine if residual tumor tissue expressed FRα. Formalin fixed paraffin embedded (FFPE) samples were sent to Ventana Translational Diagnostics CAP/CLIA Laboratory for analysis using an in-house developed assay, Ventana OptiView DAB Detection kit, and the Ventana BenchMark Ultra automated slide stainer. FRα expression was evaluated by board certified pathologists using a scoring scale 1+ (low), 2+ (medium), and 3+ (high). For the purposes of study entry, FRα expression on cell surface was required to be low, defined as >25% of cells having 1+ expression. Results: 12% (8/68) of evaluated TNBCs had moderate to high rates of FRα expression. The median age of pts screened for FRα was 53 years. Moderate to high FRα expression rates were more common in Black and Asian patients (Table 1). Conclusion: Our prospective study has demonstrated that moderate to high expression of FRα in metastatic TNBC is 12%, which is lower than previously reported. An ongoing phase II study will determine efficacy for mirvetuximab soravtansine in advanced TNBC. Acknowledgement: This study was approved and funded in part by the NCCN Oncology Research Program from general research support provided by ImmunoGen, Inc.

Background: Folate receptor alpha (FRα) is a glycosyl phosphatidylinositol (GPI)-anchored cell surface protein that binds and internalizes folate, which is a cofactor required for DNA/RNA synthesis and cell growth and proliferation. There is a marked up-regulation of FRα in many solid tumors; in contrast, FRα has a minimal expression in adult normal tissue. Mirvetuximab soravtansine is an antibody drug conjugate (ADC) consisting of a maytansinoid, N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4), conjugated to an anti-FRα antibody, M9346A. Once bound to the FRα and internalized, the anti-mitotic agents are released and inhibit tubulin polymerization and microtubule assembly, leading to cell death. Here we report the expression of FRα+ on residual tumor samples in metastatic TNBC. Methods: 68 patients (Pts) with stage IV TNBC underwent prescreening to determine if residual tumor tissue expressed FRα. Formalin fixed paraffin embedded (FFPE) samples were sent to Ventana Translational Diagnostics CAP/CLIA Laboratory for analysis using an in-house developed assay, Ventana OptiView DAB Detection kit, and the Ventana BenchMark Ultra automated slide stainer. FRα expression was evaluated by board certified pathologists using a scoring scale 1+ (low), 2+ (medium), and 3+ (high). For the purposes of study entry, FRα expression on cell surface was required to be low, defined as >25% of cells having 1+ expression. Results: 12% (8/68) of evaluated TNBCs had moderate to high rates of FRα expression. The median age of pts screened for FRα was 53 years. Moderate to high FRα expression rates were more common in Black and Asian patients (Table 1). Conclusion: Our prospective study has demonstrated that moderate to high expression of FRα in metastatic TNBC is 12%, which is lower than previously reported. An ongoing phase II study will determine efficacy for mirvetuximab soravtansine in advanced TNBC. Acknowledgement: This study was approved and funded in part by the NCCN Oncology Research Program from general research support provided by ImmunoGen, Inc.

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Corresponding Author: Thorunn Helgason, MS

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