Rina-S Generates Durable Responses in Advanced Platinum-Resistant Ovarian Cancer

Rinatabart sesutecan (Rina-S) showed clinical activity—including durable responses—in heavily pretreated patients with platinum-resistant ovarian cancer regardless of folate receptor alpha (FRα) expression level, according to findings from the phase 1/2 RAINFOL-01 study (NCT05579366) presented at the 2025 SGO Annual Meeting on Women’s Cancer.1

At 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 (ORRs) were 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% of patients in these respective arms had partial responses (PRs). Data showed disease control rates (DCRs) of 86.4% (95% CI, 65.1%-97.1%) and 88.9% (95% CI, 65.3%-98.6%) in each respective cohort.

Rina-S produced deep responses regardless of FRα expression level when administered at 120 mg/m2. The median duration of response (DOR) was not reached (NR; 95% CI, 16.3 months-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 occurred early and appeared to be durable, with 1 instance of progressive disease among patients who achieved a response since prior reports.

“Treatment with [Rina-S] was well tolerated, with manageable treatment-emergent adverse effects [TEAEs] and no new safety signals,” 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 in Boston, Massachusetts, stated in the presentation.

This phase 1/2 study assessed the efficacy and safety of Rina-S monotherapy for patients with advanced ovarian cancer. The study included an assessment of dose escalation in patients with advanced solid tumors known to express FRα in part A, monotherapy dose expansion in those with ovarian cancer and epithelial cancer in part B, monotherapy dose expansion in patients with platinum-resistant ovarian cancer 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 Rina-S 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 Measurable disease per RECIST 1.1 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 required to have received 1 to 3 prior lines of treatment for platinum-resistant ovarian cancer or up to 4 prior lines regardless of platinum 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.1 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 patients in the 100 mg/m2 cohort and 100% of those in 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 occurred in 9.1% and 5.0% of patients in 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 Rina-S will be assessed at 120 mg/m2 among patients with previously treated platinum-resistant ovarian cancer in part C of the study. Additionally, the open-label phase 3 RAINFOL-02 trial (NCT06619236) will evaluate Rina-S vs investigator’s choice of chemotherapy among patients who have received 1 to 4 prior lines of treatment for platinum-resistant ovarian cancer.

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: 2025 SGO Annual Meeting on Women’s Cancer. 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://clinicaltrials.gov/study/NCT05579366