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In patients diagnosed with endometrial cancer, expression of folate receptor-alpha (FRα) is generally associated with poor prognosis. Mirvetuximab soravtansine (Elahere®, ImmunoGen, now a part of AbbVie), an antibody drug conjugate or ADC comprising of a FRα-binding antibody, cleavable linker, and the tubulin-disrupting maytansinoid DM4, showed tolerability and single agent activity in a Phase 1 dose expansion study in FRα-positive advanced/recurrent endometrial cancer (NCT01609556).

At the recently held annual meeting of the American Association for Cancer Research (AACR), positive Phase 2 trial (NCT03835819) results of the combination of mirvetuximab soravtansine and the immune checkpoint inhibitor (ICI) Pembrolizumab (Keytruda®; Merck & Co) in the treatment of folate receptor-alpha (FR-α) positive recurrent microsatellite stable / mismatch repair proficient serous endometrial cancer were presented.[1]

According to analysts at GlobalData, a leading data and analytics company, mirvetuximab soravtansine will not only infiltrate the endometrial cancer market but also pave the way for future treatment strategies with an ADC and immunotherapy combination, says

GlobalData’s patient-based forecast reveals that the endometrial cancer market is projected to reach UD $ 7.9 billion in 2030 in the US.

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Following these results, an exploratory molecular analysis was performed to identify biomarkers as potential predictors of response. Although the response did not appear to be driven by FR-α expression, the analysis may be limited by the small sample size.

“If synergism between these two classes is confirmed, the novel combination could be utilized for other indications with overexpressed FR-α. A continued expansion study is indicated to assess whether the responses were dependent on or driven by FR-α expression. Additionally, increasing the duration of response should be a continued focus,” noted Jasminemay Barcelon, Oncology & Hematology Analyst at GlobalData.

Pembrolizumab already boasts approvals for two advanced endometrial cancer indications and in 13 other oncology indications with projected sales of US$ 22.7 billion by 2030 based on GlobalData’s analyst consensus forecast.

Mirvetuximab soravtansine recently obtained full approval as the first and only ADC for platinum-resistant ovarian cancer. Based on GlobalData’s patient-based forecast, sales of mirvetuximab soravtansine in ovarian cancer across the seven major markets (the US, France, Germany, Italy, Spain, the UK, and Japan) are predicted to reach US $ 602 million by 2030,

Mirvetuximab soravtansine holds a potential label expansion within ovarian cancer and other indications, such as non-small cell lung cancer and triple-negative breast cancer with high FR-a expression. The success of mirvetuximab soravtansine in ovarian cancer with its approved companion diagnostic, VENTANA FOLR1 assay, can serve as a model for patient stratification by biomarker.

“In terms of commercial success, pembrolizumab maintains its blockbuster status in the immune checkpoint inhibitor class despite it being oversaturated,” noted Barcelon.

“Mirvetuximab soravtansine holds a potential first-to-market advantage in endometrial cancer but will face competition from other pipeline ADC agents that may have a lower threshold for FR-α expression, increasing the treatable patient population or lower lung or ocular toxicities,” Barcelon added.

“While continued positive clinical results may lead to additional mirvetuximab soravtansine approvals and address the unmet need of the undeserved FR-α -positive patient population with an aggressive subtype of endometrial cancer, this will capture only a small patient share within this indication. However, it demonstrates the potential of combining ADCs and immunotherapies as a promising strategy to sidestep the ICI resistance and improve patients’ outcomes in solid tumors,” Barcelon concluded.

Clinical trials
First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Mirvetuximab Soravtansine in Adults With Ovarian Cancer and Other Folate Receptor 1 (FOLR1)-Positive Solid Tumors (IMGN853-0401) – NCT01609556
A Phase 2 Study of Mirvetuximab Soravtansine (IMGN853) and Pembrolizumab in Endometrial Cancer (EC) – NCT03835819

Highlights pf Prescribing Information
Mirvetuximab soravtansine (Elahere®, ImmunoGen, now a part of AbbVie) [Prescribing Information]
Pembrolizumab (Keytruda®; Merck & Co)[Prescribing Information]

VENTANA FOLR1 (FOLR1-2.1) RxDx Assay [P220006C]

Reference
[1] Rebecca L. Porter, Niya Xiong, Nabihah Tayob, Madeline Polak, Hannah Sawyer, Martin Hayes, Jeanette Gardner, Susana Campos, Neil Horowitz, Carolyn Krasner, Elizabeth K. Lee, Joyce F. Liu, Elizabeth H. Stover, Jennifer Veneris, Alexi A. Wright, Ursula A. Matulonis, Panagiotis Konstantinopoulos. 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 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT008.

Featured image: Nurse discussing a clinical trial with a patient.  Photo courtesy: © 2016 – 2024 Fotolia/Adobe. Used with permission.

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