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 adult patients with recurrent or progressive endometrial cancer who experienced disease progression on or after prior treatment with a platinum-containing regimen and a PD-(L)1 therapy.¹

Notably, Rina-S is a novel folate receptor alpha (FRα)–directed, TOPO1-inhibitor antibody-drug conjugate (ADC).

The 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. Of note, patients in the B2 cohort (n = 64) had heavily pretreated advanced or recurrent endometrial cancer and experienced disease progression on or following an anti–PD-(L)1 and platinum-based chemotherapy, and were treated with Rina-S.

“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. “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) and at 120 mg/m² (n = 34) achieved confirmed objective response rates (ORR) of 50.0% (95% CI, 28.2%-71.8%) and 47.1% (95% CI, 29.8%-64.9%), respectively.² 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 dose group, 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.

Regarding safety, treatment-emergent adverse effects (TEAEs) with Rina-S were mostly reported to be cytopenias 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 led to discontinuation of Rina-S in 4.5% and 14.3% of patients. Two fatal TEAEs occurred in the 120 mg/m² group, with none in the 100 mg/m². 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%), 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%).

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. Moreover, in the monotherapy dose expansion portion (part B), patients with advanced ovarian cancer, endometrial cancer, and non–small cell lung cancer are included. In particular, cohort B2 included patients with endometrial cancer to receive 120 mg/m² of Rina-S. Additional patients are then randomly assigned to receive either 100 mg/m² (n = 22) or 120 mg/m² (n = 21) of Rina-S.

Patients included in cohort B2 have histologically or cytologically confirmed metastatic or unresectable endometrial cancer; previously received platinum-based chemotherapy and a PD-L(1) inhibitor, unless they are ineligible or declined respective treatment; have 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. August 26, 2025. Accessed August 26, 2025. https://ir.genmab.com/news-releases/news-release-details/genmab-receives-fda-breakthrough-therapy-designation-rinatabart
2. Winter 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.303