Rina-S Wins FDA Breakthrough Therapy Designation for Advanced or Recurrent Endometrial Cancer

Rinatabart sesutecan (Rina-S) has been granted breakthrough therapy designation (BTD) by the FDA for the treatment of adults with recurrent or progressive endometrial cancer who experienced disease progression on or after treatment with a platinum-containing regimen and a PD-(L)1 therapy.1

Rina-S is a novel folate receptor α–directed, topoisomerase I–inhibitor, antibody-drug conjugate. Its BTD was supported by data from the monotherapy dose-expansion B2 cohort of the phase 1/2 RAINFOL-01 trial (NCT05579366), which is evaluating the efficacy and safety of Rina-S in patients with solid tumors. In the B2 cohort (n = 64), patients with heavily pretreated advanced or recurrent endometrial cancer with disease progression on or following an anti–PD-(L)1 and platinum-based chemotherapy were treated with Rina-S.1

“This BTD 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, executive vice president and chief development officer of Genmab, the developer of Rina-S, stated in a news release.1 “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.”

RAINFOL-01 Study Background

Preliminary data from dose-expansion cohort B2 revealed that patients with advanced or recurrent endometrial cancer treated with Rina-S at 100 mg/m2 (n = 22) or 120 mg/m2 (n = 42) achieved confirmed objective response rates of 50.0% (95% CI, 28.2%-71.8%) and 47.1% (95% CI, 29.8%-64.9%), respectively. Specifically, in the 100-mg/m2 arm, 9.1%, 40.9%, and 50.0% had a complete response, partial response, and stable disease, respectively; these responses were observed in 0%, 47.1%, and 38.2%, respectively, in the 120-mg/m2 arm, with 2.9% of patients not evaluable. Additionally, the disease control rates were 100% (95% CI, 84.6%-100.0%) and 85.3% (95% CI, 68.9%-95.0%) in the respective dosing groups.2

Regarding safety, treatment-emergent adverse effects (TEAEs) with Rina-S were mostly reported to be cytopenia and low-grade gastrointestinal AEs, which were similar among the 100-mg/m2 and 120-mg/m2 dose groups. Furthermore, TEAEs led to dose reductions in 18.2% and 16.7% of patients in the respective groups and to discontinuation of Rina-S in 4.5% and 14.3% of patients, respectively. Two fatal TEAEs occurred in the 120-mg/m2 group, with none in the 100-mg/m2 group. The most common grade 1/2 TEAEs occurring in at least 25% of patients from either group included nausea (100 mg/m2, 68.2%; 120 mg/m2, 59.5%), neutropenia (9.1%; 28.6%, respectively), anemia (18.1%; 19.1%), fatigue (50.0%; 42.9%), and vomiting (50.0%; 38.1%). The most common grade 3 or higher TEAEs occurring in at least 25% of patients included neutropenia (50.0%; 45.2%), anemia (36.4%; 47.6%), and thrombocytopenia (9.1%; 26.2%).2

RAINFOL-01 Study Design

In the dose-escalation portion of the trial (part A), patients with multiple tumor types are selected for evaluation to receive either 100 mg/m2 or 120 mg/m2 of Rina-S. In the monotherapy dose-expansion portion (part B), patients with advanced ovarian cancer, endometrial cancer, and non–small cell lung cancer are included, with cohort B2 including patients with heavily pretreated advanced or recurrent endometrial cancer.

Patients included in cohort B2 have histologically or cytologically confirmed metastatic or unresectable endometrial cancer; previously received platinum-based chemotherapy and a PD-L1 inhibitor, unless they are ineligible or declined respective treatment; an ECOG performance status of 0 or 1; measurable disease per RECIST 1.1 criteria; and adequate hematologic, hepatic, renal, and cardiac function.

References

1. Genmab receives FDA breakthrough therapy designation for rinatabart sesutecan (Rina-S) in advanced endometrial cancer (EC). News release. Genmab A/S. August 26, 2025. Accessed August 26, 2025. https://ir.genmab.com/news-releases/news-release-details/genmab-receives-fda-breakthrough-therapy-designation-rinatabart
2. Winer IS, Cloven N, Richardson DL, et al. Rinatabart sesutecan (Rina-S) for patients with advanced endometrial cancer: first disclosure from dose expansion cohort B2 of the GTC1184-01 study. J Clin Oncol. 2025;43(suppl 16):3039. doi:10.1200/JCO.2025.43.16_suppl.3039