Genmab A/S has announced 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% 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) Congress in Berlin, Germany.
Continued evaluation of single-agent Rina-S 100 mg/m2 in patients with advanced EC is ongoing in the phase 2 RAINFOL-01 trial and the phase 3 RAINFOL-03 trial.
“Women with advanced endometrial cancer are often facing a difficult path, while doctors are confronted with not having enough treatment options,” said Noelle Cloven, 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 (selected dose for phase 3 clinical trial) or 120 mg/m2 of Rina-S. In the 100 mg/m2 cohort, the confirmed ORR was 50.0%, including two CRs. Anti-tumour 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) 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, 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 gynaecologic 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, the phase 3 RAINFOL-03 trial in patients with endometrial cancer now under way and the phase 3 RAINFOL-02 trial 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.
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