2 weeks Ago
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/m 2 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/m 2 group (n = 18) were 55.
6% (95% CI, 30.8%-78.5%) and 11.
1%, respectively. The disease control rates in the 100 mg/m 2 and 120 mg/m 2 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.
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. [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/m 2 [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. 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/m 2 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/m 2 dose level.
Overall, this is a fairly well tolerated agent. Only 5 patients at the 120 mg/m 2 dose level required a dose reduction. 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.
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. 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.
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