Dr Lee on the Mechanism of Action of Rina-S in FRα+ Platinum-Resistant Ovarian Cancer

"There’s a real need to try to expand [the use of] FRα-targeted therapies to more of our patients with ovarian cancer [who have differing levels of FRα expression]. Rina-S does carry a different payload than mirvetuximab soravtansine—exatecan, which is a topoisomerase I inhibitor payload."

Elizabeth Lee, MD, a medical oncologist at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discusses the mechanism of action of rinatabart sesutecan (Rina-S; PRO1184) in patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

Rina-S is a novel folate receptor alpha (FRα)–directed antibody-drug conjugate. FRα is a validated therapeutic target in ovarian cancer and is also the target of mirvetuximab soravtansine (Elahere), an FDA-approved agent in this setting, Lee noted. However, given the heterogeneity of FRα expression in patients with ovarian cancer, there remains a clinical need to expand the applicability of FRα-targeted therapies to a broader patient population, Lee explained.

This is particularly relevant in the context of platinum-resistant ovarian cancer, where treatment options remain limited, Lee added. Rina-S uses a different cytotoxic payload than mirvetuximab soravtansine—exatecan, a topoisomerase I inhibitor—which may contribute to its activity across varying levels of FRα expression, Lee commented.

The efficacy and safety of Rina-S monotherapy in patients with advanced ovarian cancer were evaluated in the phase 1/2 RAINFOL-01 trial (NCT05579366), Lee said. Updated findings from dose expansion cohort B1, presented during the 2025 SGO Annual Meeting on Women’s Cancer, demonstrated clinical activity with Rina-S in heavily pretreated patients with platinum-resistant ovarian cancer. At a median follow-up of 46.4 months (range, 6.6-65.3) among evaluable patients in the 100 mg/m2 cohort (n = 22) and 48.1 months (range, 10.9-65.9) among evaluable patients in the 120 mg/m2 cohort (n = 18), the confirmed objective response rates were 22.7% (95% CI, 7.8%-45.4%) and 55.6% (95% CI, 30.8%-78.5%), respectively.

Notably, early and durable responses were observed in patients who received the 120-mg/m2 dose regardless of their level of FRα expression. The median duration of response was not reached (NR; 95% CI, 16.3 months-NR) in the 100 mg/m2 cohort and NR (95% CI, 40.14 months-NR) in the 120 mg/m2 group.