Elahere (mirvetuximab soravtansine)
Elahere (mirvetuximab soravtansine-IMGN853) is a novel precision cancer medicine with significant anti-cancer activity in certain ovarian cancer patients both as a single agent and in combination with Avastin (bevacizumab).1 Clinical trial results were updated at the Society for Gynecologic Oncology’s Annual Meeting on Women’s Cancer and in 2023 and the Food and Drug Administration granted accelerated approval to Elahere for the treatment of advanced platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancers that express folate receptor alpha (FRα) in November.7
About Elahere (mirvetuximab)
Elahere is an antibody drug conjugate (ADC). An ADC joins an antibody to a drug molecule that targets a key structure in cancer cells. Elahere targets the folate receptor alpha (FRα) on cancer cells and delivers anti-cancer tubulin-targeting DM4 directly to the cell.2-4
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Platinum Resistant Ovarian Cancer
Clinical trials have confirmed that Elahere delays cancer progression and prolongs overall survival duration when compared to standard single-agent chemotherapy treatment drugs used in patients with platinum-resistant ovarian cancer with high levels of folate receptor alpha (FRα) expression.
The Phase 3 MIRASOL Trial
The MIRASOL clinical trial compared Elahere with investigator’s choice of weekly chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan) in 453 patients with platinum-resistant ovarian cancer with high levels of FRα expression that has been pretreated with up to three prior lines of therapy.
Overall, 42% of patients responded to treatment with Elahere including 12 complete responses. This compares quite favorably chemotherapy which in which only 15% of patients responded and there were no complete responses. At a median follow-up of 13 months, the median survival duration for Elahere treated patients was 16.5 months compared to 12.75 months for chemotherapy.8
Patients with ovarian cancer should make sure they discuss testing for FRα. According to the study presenter “FRα status is a must know for all patients with ovarian cancer and, for those with platinum-resistant disease who test positive, I believe Elahere should be their first treatment option.”
The SORAYA Clinical Trial
The SORAYA clinical trial evaluated Elaere in patients with platinum-resistant ovarian cancer whose tumors express high levels of FRα and who had been treated with up to three prior regimens – at least one of which included Avastin (bevacizumab). The SORAYA clinical trial enrolled 106 patients with a median of three prior lines of therapy. All patients had received prior Avastin and 48% had received a prior PARP inhibitor. Overall 32% of patients experienced a response to treatment with Elahere and 5 patients experienced a complete disappearance of their cancer.6,7
Elahere + Avastin
The FORWARD II clinical trial was designed to assess the combination of Elahere and Avastin (bevacizumab) which inhibits the growth of blood vessels necessary for cancer cell growth. 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 had tumors with medium or high FRα membrane staining with immunohistochemistry PS2-positive scoring. Elahere and Avastin were administered intravenously on day 1 of an every 3-week cycle.
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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.
“These data have the potential to be transformative for ovarian cancer patients and their physicians,” said Ursula Matulonis, MD, chief of the Division of Gynecologic Oncology at Dana-Farber and co-principal investigator of the SORAYA study. “In the platinum- resistant setting and particularly in later-line treated patients, response rates with available therapy are in the single digits with significant toxicities. With an objective response rate above 30%, a duration of response of around six months, and a treatment-related discontinuation rate of 7%, Elahere shows impressive activity and tolerability for patients with platinum-resistant ovarian cancer. These data support the future of Elahere as the potential standard of care for patients with folate receptor alpha positive ovarian cancer.”
Elahere + Keytruda in Endometrial Cancer
The combination of Elahere and Keytruda (pembrolizumab) checkpoint inhibitor immunotherapy led to responses, some of which proved durable in patients with recurrent or persistent, folate receptor a (FRa)-positive mismatch repair–proficient (pMMR)/microsatellite stable (MSS) serous endometrial cancer, according to findings from a clinical trial presented at the 2024 AACR Annual Meeting.9
The combination was well tolerated with no additional side effects reported and at a median follow-up of 4.7 months, the objective response rate was 37.5% including one complete response in small group of 16 patients with recurrent cancer. Two patients who had not received prior immunotherapy, experienced a prolonged response with the combination. Studies to identify biomarkers associated with prolonged response to better identify which patients might benefit most from the treatment are ongoing.
How do doctors test for FRα?
Testing for Folate receptor alpha (FRα) is performed by immunohistochemistry on the cancer tissue that was stored from the initial biopsy and/or surgery. Currently there is not a blood test available for testing.
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References
- 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
- 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
- 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
- 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
- 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
- businesswire.com:https://www.businesswire.com/news/home/20211130005310/en/
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant?utm_medium=email&utm_source=govdelivery
- Elahere demonstrates overall survival benefit in the phase 3 MIRASOL trial in patients with FRα-positive platinum-resistant ovarian cancer. News release. ImmunoGen Inc. May 3, 2023. Accessed May 3, 2023. https://investor.immunogen.com/news-releases/news-release-details/elaherer-demonstrates-overall-survival-benefit-phase-3-mirasol
- Porter R, Xiong N, Tayob N, et al. A phase 2, two-stage study of mirvetuximab soravtansine (IMGN853) in combination with pembrolizumab in patients with microsatellite stable (MSS) recurrent or persistent endometrial cancer. Presented at: 2024 AACR Annual Meeting; April 5-10, 2024; San Diego, CA. Abstract CT008.
