Mirvetuximab soravtansine (IMGN853) in combination with Avastin (bevacizumab) yielded durable responses in patients with recurrent, platinum agnostic ovarian cancer according to the results of the final analysis of the phase 1b FORWARD II clinical trial presented during the 2021 American Society of Clinical Oncology Annual Meeting.1
Mirvetuximab is a precision cancer medicine known as an antibody drug conjugate (ADC). An ADC joins an antibody to a drug molecule that targets a key structure in cancer cells. Mirvetuximab targets the folate receptor alpha (FRα) on cancer cells and delivers tubulin-targeting DM4 directly to the cancer. Mirvetuximab has demonstrated promising activity in women with platinum-resistant ovarian cancer.2-4
The FORWARD II clinical trial was designed to assess the combination of mirvetuximab and Avastin (bevacizumab) in patients with ovarian, primary peritoneal, or fallopian tube cancer. Avastin was selected based on its known effectiveness in treating ovarian cancer. The trial enrolled patients with recurrent ovarian cancer who had previously received up to 3 prior regimens and allowed for previous treatment with Avastin. Patients also had tumors with medium or high FRα membrane staining with immunohistochemistry PS2-positive scoring. On the study, patients received 6 mg/kg of mirvetuximab that was adjusted for ideal body weight, and 15 mg/kg of Avastin, which was administered intravenously on day 1 of every 3-week cycle.
The total patient population of the study had a median duration of response to treatment of 9.7 months. Individuals with medium and high FRα expression had median response durations of 8.3 and 11.8 months, respectively. Platinum-sensitive patients had a median response duration of 12.7 months, and the researchers reported that many of the responses continue beyond 12 months. The high FRα subgroup, specifically, demonstrated a 12 month survival rate without cancer progression of 42%, and some patients’ responses are ongoing more than 2 years from treatment initiation. The mirvetuximab ADC appears promising, especially in individuals with FRα over expression and is continuing to be developed as a treatment for advanced ovarian cancer.
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1. O’Malley DM, Oaknin A, Matulonis UA, et al. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer: final analysis. J Clin Oncol. 2021;39(supple 15; abstr 5504). doi:10.1200/JCO.2021.39.15_suppl.5504
2. Moore KN, Matulonis UA, O'Malley DM, et al. Mirvetuximab soravtansine (IMGN853), a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in platinum-resistant epithelial ovarian cancer (EOC) patients (pts): Activity and safety analyses in phase I pooled expansion cohorts. J Clin Oncol. 2017;35(suppl 15):5547-5547. doi:10.1200/JCO.2017.35.15_suppl.5547
3. Moore KN, Oza AM, Oaknin A, et al. FORWARD I (GOG 3011): A Phase III study of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), versus chemotherapy in patients (pts) with platinum-resistant ovarian cancer (PROC). Ann Oncol. 2019;30(aupple 5):v403-v434. doi:10.1093/annonc/mdz250
4. O'Malley DM, Matulonis UA, Birrer MJ, et al. Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gyn Oncol. 2020;157(2):P379-385. doi:10.1016/j.ygyno.2020.01.037
5. Pujade-Lauraine E, Hilpert F, Weber D, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32(13):1302-1308. doi:10.1200/JCO.2013.51.4489