On October 18, 2025 Genmab A/S (Nasdaq: GMAB) reported updated data from cohort B2 of the Phase 1/2 RAINFOL-01 trial evaluating rinatabart sesutecan (Rina-S), an investigational folate receptor alpha (FRα)-targeted, TOPO1-inhibitor antibody-drug conjugate (ADC). The study showed that at a median study follow-up of one year, treatment with Rina-S 100 mg/m² every 3 weeks (Q3W) resulted in a 50.0% confirmed objective response rate (ORR), including two complete responses (CR), in heavily pretreated patients with advanced endometrial cancer (EC) who had progressed following platinum-based chemotherapy and an immune checkpoint inhibitor. Additionally, at a median study follow-up of one year, 63.6% of responders (including CRs) in the 100 mg/m² cohort maintained their responses and remain on treatment. The responses were observed regardless of FRα expression levels. The updated results were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Berlin, Germany.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Continued evaluation of single-agent Rina-S 100 mg/m2 in patients with advanced EC is ongoing in the Phase 2 RAINFOL-01 trial (NCT05579366) and the Phase 3 RAINFOL-03 trial (NCT07166094).
"Women with advanced endometrial cancer are often facing a difficult path, while doctors are confronted with not having enough treatment options," said Noelle Cloven, M.D., Texas Oncology Fort Worth, Sarah Cannon Research Institute, and study investigator. "That’s why these data signals with Rina-S in the updated Phase 1/2 RAINFOL-01 data are encouraging – they point to the possibility of providing more choices for patients in the future."
The B2 cohort of the Phase 1/2 RAINFOL-01 study (NCT05579366) is a dose expansion cohort evaluating the efficacy and safety of Rina-S in patients with advanced or recurrent endometrial cancer. In the study, 64 patients with heavily pretreated advanced or recurrent endometrial cancer whose disease had progressed on or after an anti-PD-(L)1 and platinum-based chemotherapy were enrolled and treated with Rina-S. Patients were administered either 100 mg/m2 (n=22) (selected dose for Phase 3 clinical trial) or 120 mg/m2 (n=42) of Rina-S. In the 100 mg/m2 cohort, the confirmed ORR was 50.0%, including two CRs. Anti-tumor activity was also observed in patients treated with Rina-S 120 mg/m2 Q3W, which resulted in 44.1% confirmed ORR and one CR. Study participants were previously treated with a median of three lines of therapy (range 1-8). Earlier results from this cohort were previously presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
Common treatment emergent adverse events (TEAEs; all grades) consisted primarily of cytopenias and low-grade gastrointestinal (GI) events. To date, there have been no signals of ocular toxicities, neuropathy, or interstitial lung disease (ILD) observed in Rina-S clinical trials consistent with prior reports. Serious TEAEs (Grade 3 or higher), occurred in 36.4% and 52.4% of patients treated with Rina-S 100 mg/m2 and 120 mg/m2, respectively. Hematologic adverse events did not require significant dose reduction and were associated with low rates of treatment discontinuation.
"With this updated data, we are seeing additional momentum behind the possibilities of Rina-S," said Tahi Ahmadi, M.D., Executive Vice President and Chief Medical Officer, Head of Experimental Medicines at Genmab. "As a wholly owned, novel antibody-drug conjugate, Rina-S reflects Genmab’s vision to accelerate our innovative, late-stage pipeline that has the potential to redefine possibilities for patients with certain gynecologic cancers."
Rina-S is advancing through late-stage development supported by a growing portfolio of clinical trials, including the ongoing Phase 1/2 RAINFOL-01 trial (NCT05579366), the Phase 3 RAINFOL-03 trial (NCT07166094) in patients with endometrial cancer now underway and the Phase 3 RAINFOL-02 trial (NCT06619236) in patients with platinum resistant ovarian cancer (PROC). The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation (BTD) to Rina-S for the treatment of adult patients with recurrent or progressive EC who have disease progression on or following prior treatment with a platinum-containing regimen and a PD-(L)1 therapy.
About the RAINFOLTM -01 Trial
RAINFOL-01 (NCT05579366) is an open-label, multicenter Phase 1/2 study, designed to evaluate the safety and efficacy of rinatabart sesutecan (Rina-S) Q3W at various doses in solid tumors that are known to express FRα. The study consists of multiple parts including Part A dose escalation; Part B tumor-specific monotherapy dose-expansion cohorts; Part C platinum-resistant ovarian cancer (PROC) cohort; Part D combination therapy cohorts; Part F a monotherapy endometrial cancer (EC) cohort.
About Endometrial Cancer
Endometrial cancer (EC) starts in the lining of the uterus, known as the endometriumi and ranks as the second most prevalent gynecologic cancer globally, with increasing incidence and mortality ratesii,iii. Patients with advanced or recurrent EC have a relatively poor prognosis and treatment options are limited for those patients who have progressed following treatment with chemotherapy and immune checkpoint inhibitor. FRα is overexpressed on multiple tumors, including EC, making it a promising therapeutic target. Anti-tumor activity with Rina-S was observed across a broad range of FRα expression, and there are currently no approved FRα-directed therapies approved for the treatment of endometrial cancer.
About Rinatabart Sesutecan (Rina-S; GEN1184)
Rinatabart sesutecan (Rina-S; GEN1184) is an investigational ADC. It is composed of a novel human monoclonal antibody directed at folate receptor α (FRα), a novel hydrophilic protease-cleavable linker, and exatecan, a topoisomerase I inhibitor payload. The clinical trial program for Rina-S continues to expand including ovarian, endometrial and other cancers of unmet need.
(Press release, Genmab, OCT 18, 2025, View Source [SID1234656746])