Rina-S Shows 50% Response Rate in Heavily Pretreated Endometrial Cancer Regardless of Target Expression
核心洞察
Rinatabart susetecan (搜索) (Rina-S) demonstrated a 50% confirmed objective response rate and 100% disease control rate at 100 mg/m2 in heavily pretreated endometrial cancer (搜索) patients.
The folate receptor alpha (搜索)-targeted antibody-drug conjugate showed efficacy regardless of FR-alpha expression levels, potentially expanding treatment access.
Patients had received a median of 3 prior therapy lines, with some having up to 8 previous treatments including platinum-based chemotherapy and immunotherapy.
Rinatabart susetecan (搜索) (Rina-S), a folate receptor alpha (搜索)-targeted antibody-drug conjugate, achieved a 50% confirmed objective response rate in heavily pretreated endometrial cancer (搜索) patients, with responses occurring regardless of target expression levels, according to updated data from the phase 1/2 RAINFOL-01 trial presented at the 2025 ESMO Congress.
Clinical Trial Results
The dose-expansion cohort B2 enrolled 64 patients with advanced endometrial cancer (搜索) who had progressed after platinum-based chemotherapy and immune checkpoint inhibitor therapy. Patients were randomized to receive either 100 mg/m2 or 120 mg/m2 of Rina-S every 3 weeks.
At the 100 mg/m2 dose level, the confirmed objective response rate reached 50%, including 2 complete responses. Notably, the treatment achieved a 100% disease control rate, encompassing patients with complete responses, partial responses, or durable stable disease. The 120 mg/m2 dose demonstrated a higher confirmed objective response rate of approximately 80%.
Patient Population and Treatment History
The study population represented a heavily pretreated group, having received a median of 3 prior lines of therapy, with some patients having undergone up to 8 previous treatment regimens. A substantial portion of patients had also received pelvic radiotherapy or other forms of radiation therapy.
"These patients who were heavily pretreated, they had received a median of 3 prior lines of therapy, but it ranged all the way up to patients who have received 7 to 8 prior lines of therapy, which is quite remarkable," said Elizabeth Lee, MD, a gynecologic oncology specialist at Dana-Farber Cancer Institute and trial investigator.
Target Expression Independence
A particularly significant finding was that responses occurred regardless of folate receptor alpha (搜索) expression levels, as measured by immunohistochemistry. This observation challenges the conventional requirement for high target expression in antibody-drug conjugate therapy.
"What we want to see is that there's very high levels of activity, even down to minimal or potentially no levels of detectable FRα (搜索)," Lee explained. "How many more women will be able to access this type of therapy that's very effective without having to meet very high levels of cut off for that protein expression?"
Dose Selection and Future Development
Based on the balance of efficacy and toxicity profiles, the 100 mg/m2 dose was selected for continued investigation. This dose level will be used in the ongoing RAINFOL-01 study enrollment and has been chosen for a planned randomized phase 3 trial in endometrial cancer (搜索) patients.
The development builds on experience with mirvetuximab soravtansine-gynx (Elahere) in ovarian cancer, with researchers applying knowledge from that program to endometrial cancer (搜索) treatment. Lee noted that endometrial cancer harbors multiple cell surface markers, including folate receptor alpha (搜索), that are overexpressed in most cases, providing a biological rationale for the targeting approach.
At a median follow-up of 1 year, the data suggest that Rina-S may address unmet medical needs in patients with advanced endometrial cancer (搜索), particularly those with low or undetectable folate receptor alpha (搜索) expression who might not qualify for other targeted therapies.