Abstract C47: Association of folate receptor alpha (FRα) expression level and clinical activity of IMGN853 (mirvetuximab soravtansine), a FRα-targeting antibody-drug conjugate (ADC), in FRα -expressing platinum-resistant epithelial ovarian cancer (EOC) patients (pts)
2015
Background: IMGN853 is a FRα-targeting ADC comprising a FRα-binding antibody conjugated with the potent maytansinoid, DM4, a tubulin-targeting agent. FRα is a membrane protein that is highly expressed in many solid tumors, particularly epithelial ovarian cancer (EOC), endometrial cancer and lung adenocarcinoma. An immunohistochemistry (IHC) assay was developed to support the FRα-expression based patient selection strategy for the clinical development of IMGN853. The assay was optimized to detect a broad dynamic range of FRα expression, allowing discrimination among weak (1+), moderate (2+) and strong (3+), levels of expression (AACR 2015 Zhao J et al). In the EOC expansion cohort of the ongoing phase 1 trial (ASCO 2015 Moore K, et al), 80% of the patients with platinum-resistant EOC screened were found to meet the FRα expression inclusion criteria of ≥ 25% of cells with at least moderate expression. Methods: Here we report the preliminary analysis evaluating the association of FRα expression with overall response rate [partial response (PR) or complete response (CR)] for the first seventeen evaluable patients with platinum-resistant EOC who received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) IV q3wk. Patients were grouped based on their FRα expression into low (25-49% of cells with ≥ moderate expression), medium (50-74% of cells with ≥ moderate expression) and high (≥ 75% of cells with ≥ moderate expression) groups. Analysis to assess the association between expression level and clinical response was performed. Results: Of the 17 patients in the analysis, 2/17 (12%) had low, 5/17 (29%) had moderate and 10/17 (59%) had high FRα expression. In the overall cohort, clinical response was observed in 9/17 patients (1 CR and 8 PRs), for an objective response rate (ORR) of 53%. When the cohort of 17 patients was grouped based on FRα expression, clinical response was observed in 0/2 low, 1/5 moderate and 8/10 high expression patients. The majority of adverse events were CTCAE grade 1 or 2, with diarrhea, blurry vision, cough, fatigue, decreased appetite, neuropathy and nausea reported in > 20% of patients. Conclusion: In these heavily pretreated platinum-resistant ovarian cancer patients, IMGN853 demonstrates promising preliminary clinical activity, with an ORR of 53% in the overall cohort and 80% in the high FRα expression subset. Preliminary analysis suggests that FRα-expression correlates well with IMGN853 activity. The association of FRα expression with IMGN853 activity will continue to be assessed as the phase I trial continues to enroll patients in the expansion cohort. Citation Format: Lainie P. Martin, Kathleen Moore, David M. O9Malley, Shelley Seward, Todd M. Bauer, Ramon Perez, Woondong Jeong, Yinghui Zhou, Joseph Ponte, Maurice Kirby, Mohammed Al-Adhami, Rodrigo Ruiz-Soto, Michael Birrer. Association of folate receptor alpha (FRα) expression level and clinical activity of IMGN853 (mirvetuximab soravtansine), a FRα-targeting antibody-drug conjugate (ADC), in FRα -expressing platinum-resistant epithelial ovarian cancer (EOC) patients (pts). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C47.
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