Why Does Rina-S Target Folate Receptor Alpha in Endometrial Cancer?

Updated data from cohort B2 of the phase 1/2 RAINFOL-01 trial (NCT05579366) demonstrate that patients with heavily pretreated, advanced endometrial cancer with indetectable folate receptor alpha (FRα) may respond to treatment with rinatabart susetecan (Rina-S), as Elizabeth Lee, MD, shared in an interview with Oncology Nursing News.

At a median follow-up of 1 year, Rina-S, an FRα-targeted TOPO1-inhibitor antibody-drug conjugate (ADC) elicited a 50.0% confirmed objective response rate (ORR) with 2 complete responses (CR) when treated with 100 mg/m² every 3 weeks in patients whose disease progressed after a platinum-based chemotherapy and an immune checkpoint inhibitor.¹

Lee, an investigator in the trial who works in gynecologic oncology at Dana-Farber Cancer Institute in Boston, Massachusetts, explained that even patients with low or no detectable FRα derived benefit from the ADC, presenting the potential to meet unmet needs in this patient population.

Transcript

We’re starting to understand more that endometrial cancer harbors a number of cell surface markers, including folate receptor alpha, that are overexpressed in most cases, in addition to other protein markers. Where Rina-S is targeting folate receptor alpha, it makes sense on a biological level.

With Rina-S, if you want to dive right into the data, this is evolving out of the ovarian cancer experience with mirvetuximab soravtansine-gynx (Elahere), and we’re bringing our knowledge, understanding, and the questions that have come from the ovarian cancer experience over to endometrial cancer.

What we want to drill down to is, does the level of expression of the target—in this case, folate receptor alpha—matter, or does it not matter? With RAINFOL-01, the B2 cohort that was presented by [Noelle Cloven, MD,] at [the 2025 ESMO Congress] intriguingly, showed responses regardless of FRα expression. This is very important.

What we want to see is that there’s very high levels of activity, even down to minimal or potentially no levels of detectable FRα, at least based on the immunohistochemistry test that we have available at this time. How many more women will be able to access this type of therapy that’s very effective without having to meet very high levels of cut off for that protein expression?

This transcript has been edited for clarity and conciseness.

Reference

1. Genmab announces new data demonstrating investigational rinatabart sesutecan (Rina-S®) achieved anti-tumor activity in heavily pretreated patients with advanced endometrial cancer. News release. Genmab. October 18, 2025. Accessed January 14, 2026. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-new-data-demonstrating-investigational