Rina-S Elicits Encouraging Antitumor Activity in Advanced Ovarian Cancer

"Treatment with [rinatabart sesutecan] was well tolerated, with manageable TEAEs and no new safety signals," according to the study authors.

Treatment with rinatabart sesutecan (Rina-S) continued to demonstrate encouraging clinical activity among patients with platinum-resistant ovarian cancer (PROC), according to findings from the phase 1/2 RAINFOL-01 study (NCT05579366) highlighted in an encore presentation at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO).¹

After a median follow-up of 46.4 months (range, 6.6-65.3) in the 100 mg/m² cohort (n = 22) and 48.1 months (range, 10.9-65.9) in the 120 mg/m² group (n = 20), the confirmed objective response rate (ORR) was 22.7% (95% CI, 7.8%-45.4%) and 55.6% (95% CI, 30.8%-78.5%) in each respective group. Additionally, 4.5% and 11.1% of patients in each respective cohort achieved complete responses (CRs), and 18.2% and 44.4% had partial responses (PRs). Data showed a disease control rate (DCR) of 86.4% (95% CI, 65.1%-97.1%) and 88.9% (95% CI, 65.3%-98.6%) in each cohort.

Rinatabart sesutecan produced deep responses regardless of folate receptor alpha (FRα) expression levels when administered at 120 mg/m². The median duration of response (DOR) was not reached (NR; 95% CI, 16.3 months to NR) in the 100 mg/m² cohort and NR (95% CI, 40.14-NR) in the 120 mg/m² group. According to the investigators, responses with the 120 mg/m² dose appeared to be early and durable, with 1 instance of progressive disease among those with a response since prior reports.

“With a median on-study follow-up of 48 weeks, [rinatabart sesutecan at 120 mg/m² every 3 weeks] continued to show encouraging antitumor activity with an ORR of 55.6%, including 4 [CRs] (2 confirmed), and a median DOR [NR], as only 1 responder progressed since prior report, in FRα unselected patients with heavily pretreated PROC,” Elizabeth K. Lee, MD, a medical oncologist in the gynecologic oncology program at Dana-Farber Cancer Institute and an instructor in Medicine at Harvard Medical School, stated with study coauthors.¹ “Treatment with [rinatabart sesutecan] was well tolerated, with manageable treatment-emergent adverse effects [TEAEs] and no new safety signals.”

Investigators of this phase 1/2 study assessed the efficacy and safety of rinatabart sesutecan monotherapy for patients with advanced ovarian cancer. The study included an assessment of dose escalation in advanced solid tumors known to express FRα in part A, monotherapy dose expansion in ovarian cancer and epithelial cancer in part B, monotherapy dose expansion in PROC during part C, and combination therapy dose expansion in part D. This presentation focused on findings from the ovarian cancer cohort during part B of the study.

In the ovarian cancer dose-expansion cohort, patients were randomly assigned 1:1 to receive rinatabart sesutecan at 100 mg/m² or 120 mg/m² once every 3 weeks. The primary end point was safety and tolerability, and antitumor activity was a secondary end point. Investigators also evaluated biomarkers as an exploratory end point.

Patients 18 years and older with histologically or cytologically confirmed metastatic or unresectable solid malignancies including ovarian cancer, endometrial cancer, non–small cell lung cancer, breast cancer, and mesothelioma were eligible for enrollment on parts A and B of the study.² Having measurable disease per RECIST v1.1 criteria for all tumor types other than pleural mesothelioma was another requirement for study entry. In the ovarian cancer cohort of part B, patients were specifically required to have 1 to 3 prior lines of treatment for PROC or up to 4 prior lines regardless of sensitivity.

The median patient age was 62.5 years (range, 42-82) in the 100 mg/m² cohort and 64.5 years (range, 37-83) in the 120 mg/m² group. The median number of prior lines of therapy was 3 in both cohorts, with the most common prior types of treatment including bevacizumab (Avastin; 90.9% vs 90.0%), PARP inhibitors (68.2% vs 60.0%), and mirvetuximab soravtansine-gynx (Elahere; 18.2% vs 20.0%). Additionally, most patients in each cohort had platinum-resistant disease (96.0% vs 90.0%) and an ECOG performance status of 1 (68.2% vs 80.0%).

Any-grade TEAEs occurred in 100% of the 100 mg/m² cohort and 100% of the 120 mg/m² cohort, with grade 3 or higher toxicities affecting 72.7% and 65.0% of patients, respectively. Additionally, TEAEs lead to dose reductions in 22.7% and 25.0% of patients and treatment discontinuation in 9.1% and 5.0% of each cohort. Granulocyte colony-stimulating factor use was reported in 36.4% and 55.0% of patients in each group.

The most common grade 1/2 TEAEs in the 100 mg/m² and 120 mg/m² cohorts, respectively, included nausea (63.7% vs 70.0%), fatigue (40.5% vs 45.0%), and vomiting (36.4% vs 40.0%). Additionally, anemia (40.9% vs 45.0%) and neutropenia (40.9% vs 45.0%) were among the most common grade 3/4 TEAEs. Investigators observed no signs of ocular toxicity, neuropathy, or interstitial lung disease.

Regarding the next steps for research, investigators noted that rinatabart sesutecan will be assessed at 120 mg/m² among patients with previously treated PROC in part C of the single-arm phase 2 RAINFOL-01 study. Additionally, the open-label phase 3 RAINFOL-02 trial (NCT06619236) will evaluate rinatabart sesutecan vs investigator’s choice of chemotherapy among patients who received 1 to 4 prior lines of treatment for PROC.

References

1. 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 the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO); March 14-17, 2025; Seattle, WA. Abstract 809034.
2. Rinatabart sesutecan (Rina-S) for advanced solid tumors (GCT1184-01/​ PRO1184-001) (PRO1184-001). ClinicalTrials.gov. Updated March 4, 2025. Accessed March 17, 2025. https://tinyurl.com/4wc23m3b