Rina-S Displays Early Efficacy in Advanced Ovarian Cancer

Elizabeth K. Lee, MD

Preliminary activity observed with the novel folate receptor alpha [FRα]-directed antibody-drug conjugate rinatabart sesutecan (Rina-S) among patients with advanced ovarian cancer in the phase 1/2 RAINFOL-01 study (NCT05579366) has stirred up excitement among investigators about the potential role of this agent in such a hard-to-treat patient population, according to Elizabeth K. Lee, MD.

Findings presented during the 2025 SGO Annual Meeting on Women’s Cancer showed that, at a median follow-up of 46.4 months (range, 6.6-65.3), patients who received 100 mg/m2 of Rina-S (n = 22) achieved a confirmed objective response rate (ORR) of 22.7% (95% CI, 7.8%-45.4%), including a 4.5% confirmed complete response (CR) rate. At a median follow-up of 48.1 months (range, 10.9-65.9), the confirmed ORR and CR rates in the 120 mg/m2 group (n = 18) were 55.6% (95% CI, 30.8%-78.5%) and 11.1%, respectively. The disease control rates in the 100 mg/m2 and 120 mg/m2 groups were 86.4% (95% CI, 65.1%-97.1%) and 88.9% (95% CI, 65.3%-98.6%), respectively.

“These are very encouraging results,” Lee said in an interview with OncLive. “We’re hoping to continue to advance the treatment landscape for patients with platinum-resistant ovarian cancer [with the development of ADCs like Rina-S].”

In the interview, Lee discussed the mechanism of action of Rina-S, reported key efficacy and safety data with this agent, and detailed how these findings support ongoing research with Rina-S in platinum-resistant ovarian cancer.

Lee is a medical oncologist in the gynecologic oncology program at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School in Boston, Massachusetts.

OncLive: What is the mechanism of action of Rina-S, and how could this agent address unmet needs for patients with platinum-resistant ovarian cancer?

Lee: Rina-S is a novel FRα-directed ADC. We’re all very familiar with FRα, which is a validated therapeutic target and is the target for mirvetuximab soravtansine [Elahere], which is an FDA-approved agent in this space. [However], for our patients who have differing levels of FRα expression, there’s a real need to try to expand [the use of] FRα-targeted therapies to more of our patients with ovarian cancer.

Especially in platinum-resistant ovarian cancer, the treatment options are quite limited. Rina-S does carry a different payload than mirvetuximab soravtansine, exatecan, which is a topoisomerase I inhibitor payload.

What updated efficacy data from RAINFOL-01 were presented at the meeting?

[During] the 2025 SGO Annual Meeting on Women’s Cancer we presented results from cohort b1 of [the] dose-expansion [phase. These were patients with predominantly platinum-resistant ovarian cancer; these are epithelial ovarian cancers. This was a heavily pretreated patient population with a median of 3 [range, 1-5] prior lines of therapy. We’re looking for more effective therapies in these settings.

We presented updated data with [approximately] 48 weeks of follow-up, compared with a prior report with [approximately] 24 weeks of follow-up. With prolonged follow-up, we saw that Rina-S at the 120 mg/m2 [dose level] showed a very encouraging confirmed ORR of 55.6% with 2 confirmed CRs and a total of 4 CRs. [Additionally], with the longer duration of follow-up, the median duration of response has not yet been reached. We’re very encouraged by the findings so far.

Were there any notable safety concerns with Rina-S?

With a newer drug, the safety profile is important to pay attention to for our patients’ quality of life and for thinking about combinations. We predominantly saw grade 1 or 2 cytopenia and gastrointestinal [toxicities]. Notably, 45% of patients did experience grade 3 or 4 anemia and neutropenia at the 120 mg/m2 dose level, but this was well managed with granulocyte-colony stimulating factor, which was allowed to be used reactively. This occurred in 55% of patients at the 120 mg/m2 dose level. Overall, this is a fairly well tolerated agent. Only 5 patients at the 120 mg/m2 dose level required a dose reduction.

In light of these findings, what next steps are planned for the development of Rina-S in ovarian cancer?

The dose-expansion data we presented were in a limited subset of patients. Part C of RAINFOL-01 is ongoing and is enrolling approximately 100 patients with advanced ovarian cancer. This will provide us with a bit more data. With the encouraging results that we’ve seen so far, we have opened the randomized phase 3 RAINFOL-02 trial [NCT06619236] comparing Rina-S with investigator’s choice of chemotherapy.

What do you want your colleagues to take away from your presentation?

The ADC space is so exciting, and there are now many options for patients with platinum-resistant ovarian cancer. I always try to get newer and more effective agents to my patients. I want to encourage [clinicians] to consider trials early for their patients, especially as we’re starting to see these ADCs being moved up in the recurrent setting. [Although] there may be limitations on the number of prior lines [of therapy patients could have received to enroll], we want to try to give these kinds of opportunities on clinical trials.

Reference

Lee EK, Yeku O, Winer I, et al. Rinatabart sesutecan (Rina-S) for patients with advanced ovarian cancer: results from dose expansion cohort B1 of a phase 1/2 study. Presented at: 2025 SGO Annual Meeting on Women’s Cancer. March 14-17, 2025; Seattle, WA. Abstract 809034.