New drug for endometrial cancer wins FDA’s breakthrough status
Rina-S is being tested in a study that includes 64 adults in the US and China
The U.S. Food and Drug Administration (FDA) has awarded breakthrough therapy status to rinatabart sesutecan (Rina-S), an investigational treatment for certain cancers, including advanced endometrial cancer.
The designation is intended to accelerate the development of new investigational therapies for serious diseases, for which early clinical evidence suggests they may be better than available treatments. Rina-S is being developed by Genmab.
“This breakthrough therapy designation underscores the future potential of Rina-S as a treatment option for women diagnosed with advanced endometrial cancer, who face a poor prognosis after progressing on standard of care treatment,” Judith Klimovsky, MD, Genmab’s executive vice president and chief development officer, said in a press release.
Endometrial cancer affects the cells lining the uterus, known as the endometrium, and is one of the most common gynecological cancers. There are limited treatment options for advanced or recurrent endometrial cancer after it progresses following treatment with chemotherapy and an immune checkpoint inhibitor, a therapy that blocks specific proteins to help the immune system attack the tumor cells.
What is Rina-S?
Rina-S, also called GEN1184, is an antibody-drug conjugate that targets the folate receptor alpha (FR-alpha). It combines an antibody directed against FR-alpha with exatecan, a potent molecule that disrupts DNA repair and induces tumor cell death. FR-alpha is over-expressed in endometrial cancer and other tumor types. By binding to FR-alpha on the surface of tumor cells, Rina-S delivers its cytotoxic payload directly into the cells, leading to selective tumor killing.
The treatment’s safety and anti-tumoral activity are being tested in the Phase 1/2 RAINFOL-01 trial (NCT05579366), which is enrolling adults with ovarian, endometrial, and other tumors in the U.S. and China. The study has enrolled 64 patients with heavily pretreated advanced or recurrent endometrial cancer, whose disease had progressed during or after platinum-based chemotherapy and anti–PD-L1 immunotherapy. The participants received a median of three prior lines of therapy and were treated with Rina-S at one of two dosing regimens, 100 or 120 milligrams per square meter (mg/m²), every three weeks.
About 50% of the patients responded to treatment, with two in the low-dose group achieving a complete response, which means all the target lesions completely disappeared and there were no new lesions or disease progression. The effect was sustained, with a median follow-up of 7.7 months in the low-dose group and 9.8 months in the high-dose group.
The most reported adverse events included gastrointestinal issues — diarrhea, constipation, nausea, vomiting, and decreased appetite — shortness of breath, urinary tract infections, headache, and fatigue. Treatment-related serious adverse events were observed in 31.8% of those in the low-dose group and 50% in the high-dose group.
Other solid tumor types are also being evaluated, including certain types of ovarian, lung, and breast cancers. A Phase 3 trial (NCT06619236) is testing Rina-S in women with platinum-resistant ovarian cancer and Phase 3 trial for endometrial cancer is planned.
“Rina-S reinforces Genmab’s determination to advance wholly owned antibody medicines in areas long overdue for innovation and our commitment to driving a strong clinical development program to help redefine what’s possible to treat gynecologic cancers,” Klimovsky said.
