Phase I/II RAINFOL-01 Trial Results Lead to FDA Breakthrough Designation for Genmab’s Rina-S for Advanced Endometrial Cancer

The FDA has granted Breakthrough Therapy Designation (BTD) to Genmab’s Rina-S (rinatabart sesutecan) for the treatment of advanced endometrial cancer (EC) in patients whose disease has progressed following platinum-based chemotherapy and PD-L1 therapy. Rina-S is an investigational folate receptor alpha (FRα)-directed, TOPO1-inhibitor antibody-drug conjugate (ADC).

The BTD was based on data from cohort B2 of the Phase I/II RAINFOL-01 trial (NCT05579366), which demonstrated encouraging clinical activity.¹

“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,” said Judith Klimovsky, MD, EVP, chief development officer, Genmab, in a press release. “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.”

Inside the RAINFOL-01 Trial

• The open-label, multicenter RAINFOL-01 trial evaluated the efficacy and safety of Rina-S in approximately 569 patients with solid tumors that are known to express FRα.
• The trial was structured into multiple parts to address different patient populations and treatment strategies:
  • Part A evaluated Rina-S as monotherapy across several cohorts.
  • Part B focused on tumor-specific monotherapy dose-expansion cohorts.
  • Part C enrolled patients with platinum-resistant ovarian cancer.
  • Part D investigated Rina-S in combination therapy settings.
  • Part F specifically studied a monotherapy cohort in endometrial cancer.
  • Part K (US only) assessed a monotherapy QTc substudy cohort in patients with high-grade ovarian cancer.
• The B2 cohort consisted of 64 patients with heavily pretreated advanced or recurrent EC.²
  • Patients in B2 were treated with 100 mg of Rina-S every three weeks (Q3W).³
• The primary endpoint of Part B was the incidence of treatment-emergent adverse events (TEAEs).
• Key secondary endpoints included best overall response, overall response rate (ORR), disease control rate, progression-free survival, duration of response (DOR), and peak plasma concentration.²

Results from the B2 Cohort

• Results showed that treatment with Rina-S Q3W resulted in a 50% confirmed ORR.
• After a median follow-up of 7.7 months, median DOR was not reached.
• At the 120 mg dose, Rina-S demonstrated a confirmed ORR of 47.1% with a median follow-up of 9.8 months.
• TEAEs were consistent with expectations for this patient population, with the most common being diarrhea, dyspnea, urinary tract infections, headache, constipation, decreased appetite, vomiting, fatigue, and nausea.
• Grade ≥3 serious adverse events occurred in 31.8% of patients at the 100 mg dose and 50.0% at the 120 mg dose.³

The Broader Burden of Endometrial Cancer

• According to the American Cancer Society, EC is the fourth most common cancer for women in the United States.
• EC is most common in post-menopausal women, with a median diagnosis age of 60 years. It is rare in women under 45 years of age.
• Since the mid-2000s, the incidence of EC has increased by 1% per year.⁴

“Advanced stage and recurrent endometrial cancer often lead to resistance to standard of care options. When this occurs, prognosis worsens and treatment options become increasingly limited, leaving patients and clinicians to navigate difficult decisions,” said Ira Winer, MD, PhD, FACOG, RAINFOL-01 trial investigator, professor, division of gynecologic oncology and Phase I developmental therapeutics, Karmanos Cancer Institute, Wayne State University, in a June press release. “These Phase I/II results demonstrate encouraging data with Rina-S in this patient population and support its further development as a potential therapy for patients with advanced and recurrent endometrial cancer.”³

References

1. Genmab Receives FDA Breakthrough Therapy Designation for Rinatabart Sesutecan (Rina-S®) in Advanced Endometrial Cancer (EC). Genmab. August 26, 2025. Accessed August 26, 2025. https://ir.genmab.com/news-releases/news-release-details/genmab-receives-fda-breakthrough-therapy-designation-rinatabart
2. Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/​ PRO1184-001) (RAINFOL-01). Clinicaltrials.gov. Accessed August 26, 2025. https://clinicaltrials.gov/study/NCT05579366?term=RAINFOL-01%20&rank=1
3. Genmab Announces Investigational Rinatabart Sesutecan (Rina-S®) Demonstrates Encouraging Anti-Tumor Activity in Heavily Pretreated Patients with Advanced Endometrial Cancer in Phase 1/2 RAINFOL™-01 Trial. BusinessWire. June 2, 2025. Accessed August 26, 2025. https://www.businesswire.com/news/home/20250602832626/en/Genmab-Announces-Investigational-Rinatabart-Sesutecan-Rina-S-Demonstrates-Encouraging-Anti-Tumor-Activity-in-Heavily-Pretreated-Patients-with-Advanced-Endometrial-Cancer-in-Phase-12-RAINFOL-01-Trial
4. Key Statistics for Endometrial Cancer. American Cancer Society. Accessed August 26, 2025. https://www.cancer.org/cancer/types/endometrial-cancer/about/key-statistics.html