Rina-S earned breakthrough remedy designation from the FDA for sufferers with superior endometrial most cancers whose illness has worsened after platinum-based chemotherapy.
The U.S. Meals and Drug Administration (FDA) has granted breakthrough remedy designation to rinatabart sesutecan (Rina-S), an investigational antibody-drug conjugate (ADC), for sufferers with superior endometrial most cancers whose illness has worsened after platinum-based chemotherapy and PD-(L)1 immunotherapy, in line with a information launch from Genmab.
The designation is predicated on outcomes from the continued Part 1/2 RAINFOL-01 trial, which is evaluating Rina-S as a single-agent remedy.
Breakthrough remedy designation is meant to hurry the event and overview of therapies that will considerably enhance outcomes for sufferers going through severe or life-threatening situations. For ladies with superior or recurrent endometrial most cancers, present choices are restricted as soon as normal remedies fail, and prognosis is commonly poor.
“This breakthrough remedy designation underscores the long run potential of Rina-S as a remedy choice for ladies recognized with superior endometrial most cancers, who face a poor prognosis after progressing on normal of care remedy,” stated Dr. Judith Klimovsky, govt vp and chief improvement officer at Genmab.
RAINFOL-01 Trial Outcomes Present Responses With Rina-S in Superior Endometrial Most cancers
Information from cohort B2 of the part 1/2 RAINFOL-01 trial have been offered on the 2025 American Society of Medical Oncology (ASCO) Annual Assembly. The research included 64 closely pretreated sufferers with superior or recurrent endometrial most cancers whose illness had progressed after chemotherapy and immunotherapy.
Sufferers handled within the 100 mg/m2 group (22 sufferers) achieved a 50% confirmed goal response charge (ORR), together with two full responses. The median period of response was not reached after a median follow-up of seven.7 months, suggesting responses could also be long-lasting.
Within the 120 mg/m2 group (42 sufferers), the confirmed ORR was 47.1%, and the median period of response was additionally not reached after a median follow-up of 9.8 months. On common, sufferers had beforehand acquired three traces of remedy (starting from one to eight).
“These part 1/2 outcomes display encouraging information with Rina-S on this affected person inhabitants and assist its additional improvement as a possible remedy for sufferers with superior and recurrent endometrial most cancers,” stated Dr. Ira Winer, research investigator and professor of gynecologic oncology on the Karmanos Most cancers Institute, Wayne State College.
Furthermore, remedy with Rina-S was usually properly tolerated. The most typical unintended effects (all grades) included diarrhea, shortness of breath, urinary tract infections, headache, constipation, decreased urge for food, fatigue, nausea and vomiting.
Severe unintended effects of grade 3 (extreme) or increased occurred in 31.8% of sufferers within the 100 mg/m2 group and 50% within the 120 mg/m² group. Importantly, hematologic unintended effects have been manageable, with low charges of remedy discontinuation. Not like another ADCs, Rina-S was not linked to eye issues, nerve harm or interstitial lung illness — toxicities that may restrict use of different medication on this class.
How Rina-S Targets Folate Receptor Alpha in Endometrial Most cancers Therapy
Rina-S is designed to focus on folate receptor alpha (FRα), a protein that’s usually overexpressed on endometrial tumors. It hyperlinks a monoclonal antibody to exatecan, a chemotherapy payload, utilizing a cleavable linker. As soon as certain to most cancers cells, the drug is taken contained in the cell, the place it releases the chemotherapy agent to kill the tumor from inside.
“Testing for FRα is now a part of our normal of care testing, and actually that ought to be thought-about. [I do this] in my medical observe for anybody with a recurrence; I additionally have a tendency to do that for some with superior illness on the [time of] prognosis,” Dr. Elizabeth Okay. Lee, of Dana-Farber Most cancers Institute, stated in a previous interview with CURE.
This focused design goals to maximise anti-tumor exercise whereas minimizing hurt to wholesome cells. Notably, the research noticed responses throughout a variety of FRα expression ranges, which can imply the remedy may gain advantage a broad inhabitants of sufferers. At present, no FRα-targeted remedies are authorized for endometrial most cancers.
What’s Subsequent for Rina-S: Part 3 Trials in Endometrial and Ovarian Most cancers
Rina-S continues to be evaluated within the part 1/2 RAINFOL-01 trial, and a part 3 trial in endometrial most cancers is deliberate. As well as, the remedy is being studied in ovarian most cancers within the part 3 RAINFOL-02 trial and in a number of different cancers of unmet want.
Endometrial most cancers is the second most typical gynecologic most cancers worldwide, and its incidence and mortality are rising. Sufferers with superior or recurrent illness usually have few choices as soon as chemotherapy and immunotherapy cease working.
“Rina-S represents the type of innovation that defines our focus at Genmab — growing wholly owned, novel antibody medicines which have the potential to remodel the remedy of most cancers,” Klimovsky concluded.
References
- “Genmab Receives FDA Breakthrough Remedy Designation for Rinatabart Sesutecan (Rina-S®) in Superior Endometrial Most cancers (EC),” by Genmab. Information launch; Aug. 26, 2025.
- “Genmab Declares Investigational Rinatabart Sesutecan (Rina-S®) Demonstrates Encouraging Anti-Tumor Exercise in Closely Pretreated Sufferers with Superior Endometrial Most cancers in Part 1/2 RAINFOL™-01 Trial,” by Genmab. Information launch; June 2, 2025.
- “Rina-S Generates Antitumor Exercise in Closely Pretreated Ovarian Most cancers,” by Dr. Elizabeth Okay. Lee. CURE. VIdeo; March 27, 2025.
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