Genmab Reports Promising New Data Showing Rina-S® Demonstrates Strong Anti-Tumor Activity in Advanced Endometrial Cancer
Genmab A/S (Nasdaq: GMAB) announced new and encouraging results from its Phase 1/2 RAINFOL™-01 clinical trial evaluating rinatabart sesutecan (Rina-S®), an investigational folate receptor alpha (FRα)-targeted antibody-drug conjugate (ADC). Updated data from cohort B2 of the study revealed that Rina-S achieved a 50% confirmed objective response rate (ORR), including two complete responses (CRs), among heavily pretreated patients with advanced endometrial cancer (EC). These results were shared at the European Society for Medical Oncology (ESMO) Congress held in Berlin, Germany.
After a median follow-up of one year, 63.6% of responders in the 100 mg/m² dose cohort (the dose selected for further development) maintained their response and remain on treatment, indicating durable clinical benefit. Importantly, these anti-tumor responses were observed regardless of FRα expression levels, suggesting broad potential activity across patient subgroups.
Study Overview and Patient Population
The RAINFOL-01 trial (NCT05579366) is a multi-cohort, Phase 1/2 study designed to evaluate the safety, tolerability, and efficacy of Rina-S as a single agent in patients with advanced or recurrent cancers expressing folate receptor alpha. Cohort B2 specifically enrolled 64 patients with heavily pretreated advanced or recurrent endometrial cancer who had experienced disease progression after both platinum-based chemotherapy and immune checkpoint inhibitor therapy (anti–PD-(L)1).
Participants were assigned to receive either 100 mg/m² (n=22) or 120 mg/m² (n=42) of Rina-S administered every three weeks (Q3W). Most patients had undergone multiple prior lines of therapy, with a median of three (range 1–8), underscoring the treatment-resistant nature of this population.
The 100 mg/m² dose was selected for further evaluation in late-stage studies based on the overall efficacy and safety profile observed in this trial. At this dose, Rina-S achieved a 50% confirmed ORR, which included two complete responses. The 120 mg/m² cohort also demonstrated notable activity, showing a 44.1% confirmed ORR with one complete response. These outcomes provide additional support for the potential of Rina-S to offer meaningful clinical benefit in a patient group with limited treatment options.
Safety and Tolerability
Across both dose levels, Rina-S demonstrated a manageable safety profile consistent with earlier reports. The most common treatment-emergent adverse events (TEAEs) were hematologic in nature—primarily cytopenias—and low-grade gastrointestinal (GI) events, such as nausea or diarrhea. These were generally manageable with standard supportive care.
Notably, there were no reported cases of ocular toxicity, neuropathy, or interstitial lung disease (ILD), adverse effects sometimes associated with other ADC therapies. This absence is a significant differentiating factor and may contribute to better long-term tolerability.
Serious (Grade ≥3) treatment-related adverse events occurred in 36.4% of patients in the 100 mg/m² cohort and 52.4% in the 120 mg/m² cohort. However, hematologic toxicities rarely required major dose modifications or discontinuation, further supporting Rina-S’s manageable safety profile.
Expert and Company Perspectives
“Women with advanced endometrial cancer often face a challenging journey, compounded by limited treatment options after standard therapies fail,” said Noelle Cloven, M.D., of Texas Oncology Fort Worth and the Sarah Cannon Research Institute, who serves as an investigator in the study. “These new Rina-S data are encouraging because they point toward a potential new therapy that could expand future treatment choices for patients with this difficult disease.”
Genmab’s Executive Vice President and Chief Medical Officer, Tahi Ahmadi, M.D., emphasized the broader significance of these results. “With this updated data, we are seeing growing momentum behind Rina-S and its potential to reshape treatment possibilities,” Ahmadi said. “As a wholly owned, novel ADC, Rina-S is a clear example of Genmab’s commitment to advancing innovative therapies and building a robust late-stage pipeline focused on improving outcomes for patients with gynecologic cancers.”
Advancing Rina-S Through Clinical Development
The development of Rina-S continues across multiple global clinical programs. In addition to the ongoing Phase 1/2 RAINFOL-01 trial, Genmab is conducting two late-stage studies:
- Phase 3 RAINFOL-03 (NCT07166094) — evaluating Rina-S as a single agent in patients with advanced endometrial cancer.
- Phase 3 RAINFOL-02 (NCT06619236) — assessing Rina-S in patients with platinum-resistant ovarian cancer (PROC).
Both studies are expected to further clarify Rina-S’s role as a potential treatment for patients with limited therapeutic options in gynecologic cancers.
The U.S. Food and Drug Administration (FDA) recently recognized the potential of Rina-S by granting it Breakthrough Therapy Designation (BTD) for the treatment of adult patients with recurrent or progressive endometrial cancer whose disease has advanced following prior platinum-containing chemotherapy and PD-(L)1 therapy. This designation is intended to expedite the development and regulatory review of drugs that may offer substantial improvement over existing therapies on clinically significant endpoints.
About Rina-S® (Rinatabart Sesutecan)
Rina-S® is an investigational antibody-drug conjugate (ADC) designed to target folate receptor alpha (FRα), which is frequently expressed on the surface of certain gynecologic cancers, including endometrial and ovarian tumors. The therapy combines a highly specific monoclonal antibody with a topoisomerase I inhibitor (TOPO1) payload via a cleavable linker, enabling targeted delivery of the cytotoxic agent directly to cancer cells while minimizing damage to healthy tissues.
By exploiting the overexpression of FRα in tumor cells, Rina-S is designed to maximize anti-tumor efficacy while maintaining a favorable safety profile. The promising results from RAINFOL-01 further validate the scientific rationale behind this approach and support continued exploration across multiple cancer types.
Endometrial cancer is among the most common gynecologic malignancies, and recurrence after standard therapy often leaves patients with few effective options. The emergence of targeted therapies like Rina-S represents an important step toward addressing this unmet medical need.
The combination of durable responses, manageable safety, and activity independent of FRα expression positions Rina-S as a potential new therapeutic option in the evolving landscape of endometrial cancer treatment. With pivotal trials underway and regulatory momentum building, Genmab’s Rina-S program underscores the company’s growing leadership in next-generation ADC development and its commitment to transforming outcomes for women facing advanced cancers.
