Novel Antibody-Drug Conjugate Demonstrates Durable Responses in Patients With Platinum-Resistant Ovarian Cancer

An investigational antibody-drug conjugate demonstrated clinically meaningful and durable responses in patients with platinum-resistant ovarian cancer, including patients whose tumors had low or no expression of folate receptor alpha (FRalpha), according to findings from the Phase 1/2 RAINFOL-01 clinical trial.

The results, presented at the 2026 International Gynecologic Cancer Society (IGCS) Congress in Montreal, evaluated rinatabart sesutecan (Rina-S), an investigational FRalpha-targeted antibody-drug conjugate, in patients with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer. The data was presented by Elizabeth K. Lee, MD, a medical oncologist in the Gynecologic Oncology Program at Dana-Farber Cancer Institute, and the lead investigator on the study.

Among 109 patients treated with Rina-S, 45.9% had a confirmed objective response, including five complete responses. The median duration of response was 12.1 months, with 51% of patients who responded remaining in response at one year. Median progression-free survival was 9.5 months.

“Platinum-resistant ovarian cancer is a difficult-to-treat disease, and patients often have limited treatment options as the disease progresses through successive lines of therapy,” said Lee. “Seeing responses that were both clinically meaningful and durable in this heavily pretreated population is encouraging. The activity observed across different levels of FRalpha expression is also particularly important as we continue to investigate new approaches for patients with ovarian cancer.”

The RAINFOL-01 study included patients with platinum-resistant high-grade serous ovarian, primary peritoneal, or fallopian tube cancer who had received one to three prior lines of therapy. Patients whose most recent treatment was mirvetuximab could have received up to four prior lines. More than half of the patients in the study had received three or four prior lines of treatment. All participants had previously received bevacizumab and a taxane; approximately half had received a PARP inhibitor, and one-third had previously received mirvetuximab soravtansine.

Antitumor activity was observed regardless of FRalpha expression, including among patients with low FRalpha expression and those whose tumors did not express FRalpha. Responses were also observed regardless of prior treatment with mirvetuximab and for patents that had received mirvetuximab treatment the median doration of response was 13.1 months.

Rina-S is designed to deliver a topoisomerase I inhibitor directly to cancer cells through an antibody that targets FRalpha. The investigational treatment combines a monoclonal antibody directed against FRalpha with a cleavable linker and exatecan, a topoisomerase I inhibitor payload.

The most commonly reported side effects included fatigue and gastrointestinal symptoms, including nausea, vomiting, constipation, decreased appetite, and abdominal pain. Hematologic side effects included anemia, neutropenia, and thrombocytopenia. Treatment-related adverse events led to treatment discontinuation in only 1.8 % of patients. No safety signals for ocular toxicity, peripheral neuropathy, interstitial lung disease, or stomatitis were observed in the study.

“These findings add to the growing evidence that antibody-drug conjugates may offer new strategies for treating ovarian cancer, particularly for patients whose disease has become resistant to standard therapies,” said Lee. “Further studies are needed to determine the role Rina-S may ultimately have in the treatment of ovarian cancer.”

The RAINFOL-01 study is an open-label, multicenter Phase 1/2 clinical trial evaluating the safety and efficacy of Rina-S at different doses in patients with selected solid tumors. The study includes patients with a range of FRalpha expression levels and consists of multiple treatment cohorts. Rina-S is being studied in additional clinical trials in ovarian cancer and other cancers. A randomized phase 3 trial, RAINFOL-02, for which Lee is the national co-principal investigator, is currently enrolling patients.