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

• New data showed that rinatabart sesutecan (Rina-S^®) 100 mg/m² led to a confirmed objective response rate (ORR) of 50.0 percent, including two complete responses (CR), and median duration of response (mDOR) was not reached after a median follow-up of 7.7 months
• Continued evaluation of single-agent Rina-S 100 mg/m² in patients with advanced endometrial cancer (EC) is ongoing in the Phase 2 RAINFOL™-01 trial and will be further evaluated in a planned Phase 3 trial

COPENHAGEN, Denmark--(BUSINESS WIRE)-- Genmab A/S (Nasdaq: GMAB) announced today new 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 with a median on-study follow-up of 7.7 months, treatment with Rina-S 100 mg/m² every 3 weeks (Q3W) resulted in a 50.0 percent confirmed objective response rate (ORR), including two complete responses (CR), in heavily pre-treated advanced endometrial cancer (EC) patients who experienced disease progression on or after treatment with platinum-based chemotherapy and an immune checkpoint inhibitor. The median duration of response (mDOR) was not reached. These data are from the endometrial cancer monotherapy dose expansion B2 cohort of the multi-part RAINFOL-01 trial evaluating the safety and efficacy of Rina-S in solid tumors and were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

“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, M.D., Ph.D., FACOG, study investigator and Professor, Division of Gynecologic Oncology and Phase I Developmental Therapeutics at the Karmanos Cancer Institute, Wayne State University. “These Phase 1/2 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.”

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) or 120 mg/m² (n=42) of Rina-S. In the 100 mg/m² cohort, the confirmed ORR was 50.0 percent, including two CRs. Anti-tumor activity was also observed in patients treated with Rina-S 120 mg/m² Q3W, which resulted in 47.1 percent confirmed ORR. The mDoR was not reached after a median follow-up of 7.7 months in the 100 mg/m² cohort and a median follow-up of 9.8 months in the 120 mg/m² cohort. Median age was 67.0 years and 69.5 years in the 100 mg/m² and 120 mg/m² cohorts, respectively. Study participants were previously treated with a median of three lines of therapy (range 1-8).

Common treatment emergent adverse events (TEAEs; all grades) included diarrhea, shortness of breath (dyspnea), urinary tract infection, headache, constipation, decreased appetite, vomiting, fatigue and nausea. Serious TEAEs (Grade 3 or higher) occurred in 31.8 percent and 50.0 percent of patients treated with Rina-S 100 mg/m² and 120 mg/m², respectively. Hematologic adverse events were manageable without significant dose reduction and with low rates of treatment discontinuation. No signals of ocular toxicities, neuropathy or Interstitial Lung Disease (ILD) were observed. Ocular toxicities and ILD are often reported as adverse events associated with ADCs ^i,ii,iii,iv.

“Rina-S represents the kind of innovation that defines our focus at Genmab, which is to develop wholly owned, novel antibody-based medicines that have the potential to transform the treatment of cancer and address an unmet need, including for patients with advanced endometrial cancer,” said Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer of Genmab. “The encouraging early signals in endometrial cancer underscore our deep commitment to making a meaningful impact for women with gynecologic cancers, where treatment advances have long lagged behind the need.”

About the RAINFOL^TM -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 monotherapy cohorts; Part B tumor-specific monotherapy dose-expansion cohorts; Part C platinum-resistant ovarian cancer (PROC) cohort; Part D combination therapy cohorts; and Part F a monotherapy endometrial cancer (EC) cohort.

About Endometrial Cancer
Endometrial cancer (EC) ranks as the second most prevalent gynecologic cancer globally, with increasing incidence and mortality rates^v,vi, highlighting the need for effective management strategies. 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-targeting therapies approved for the treatment of endometrial cancer.

EC starts in the lining of the uterus, known as the endometrium.^vii Patients with advanced or recurrent endometrial cancer have a high unmet need. Most (64-74 percent) patients with EC experience disease progression on immune checkpoint inhibitors (ICI) plus chemotherapy irrespective of biomarker status. Treatment options after progression on an ICI-regimen are very limited and consist of single-agent chemotherapy (ORR <16 percent and median progression-free survival [PFS] <5 months).

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. In January 2024, the U.S. Food and Drug Administration granted Fast Track designation to Rina-S for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

Rina-S is advancing through late-stage development, supported by a growing portfolio of Phase 2 and Phase 3 trials, including further evaluation of single-agent Rina-S in patients with advanced endometrial cancer in Part F of the ongoing RAINFOL™-01 trial and in a planned Phase 3 trial.

The safety and efficacy of rinatabart sesutecan has not been established. Please visit www.clinicaltrials.gov for more information.

About Genmab
Genmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For more than 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab’s vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO) antibody medicines^®.

Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com and follow us on LinkedIn and X.

This Media Release contains forward looking statements. The words “believe,” “expect,” “anticipate,” “intend” and “plan” and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with preclinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab’s most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab’s most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Media Release nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

Genmab A/S and/or its subsidiaries own the following trademarks: Genmab^®; the Y-shaped Genmab logo^®; Genmab in combination with the Y-shaped Genmab logo^®; HuMax^®; DuoBody^®; HexaBody^®; DuoHexaBody^®, HexElect^® and KYSO^®.

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i Li BT, Meric-Bernstam F, Bardia A, et al. Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study. Lancet Oncol 2024;25(6):707-719. (In eng). DOI: 10.1016/s1470-2045(24)00140-2.

ii Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med 2023;389(23):2162-2174. (In eng). DOI: 10.1056/NEJMoa2309169.

iii Vergote I, González-Martín A, Fujiwara K, et al. Tisotumab vedotin as second- or third-line therapy forrecurrent cervical cancer. N Engl J Med 2024;391(1):44-55. (In eng). DOI: 10.1056/NEJMoa2313811.

iv Hackshaw MD, Danysh HE, Singh J, et al. Incidence of pneumonitis/interstitial lung disease induced by HER2-targeting therapy for HER2-positive metastatic breast cancer. Breast Cancer Res Treat 2020;183(1):23-39. (In eng). DOI: 10.1007/s10549-020-05754-8.

v Ferlay J, Ervik M, Lam F, et al. Global cancer observatory: Cancer today (version 1.1). International Agency for Research on Cancer. 05/28/2024 (https://gco.iarc.who.int/today).

vi Concin N, Matias-Guiu X, Vergote I, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2021;31(1):12-39. (In eng). DOI: 10.1136/ijgc-2020-002230.

vii Mayo Clinic. Endometrial Cancer. https://www.mayoclinic.org/diseases-conditions/endometrial-cancer/symptoms-causes/syc-20352461. Accessed May 2025.

 

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