Genmab's rinatabart sesutecan (Rina-S), an investigational folate receptor-alpha (FRα)-targeted antibody-drug conjugate (ADC), has shown encouraging anti-tumor activity in heavily pretreated patients with advanced ovarian cancer. Data from the Phase 1/2 study, presented at the European Society of Medical Oncology (ESMO) Congress 2024, revealed a confirmed objective response rate (ORR) of 50.0% in patients treated with Rina-S at 120 mg/m2 once every three weeks (Q3W), irrespective of FRα expression levels.
Phase 1/2 Trial Results
The Phase 1/2 study randomized 42 previously-treated patients with advanced ovarian cancer to Rina-S at either 100 mg/m2 (n=22) or 120 mg/m2 (n=20). A significant majority of patients in both groups were identified as having platinum-resistant ovarian cancer (PROC): 95% in the 120 mg/m2 group and 90.9% in the 100 mg/m2 group. The confirmed ORR in the 100 mg/m2 group was 18.2%, compared to 50.0% in the 120 mg/m2 group. Notably, in the 120 mg/m2 arm, one patient achieved a complete response, and eight patients experienced partial responses. The disease control rate (DCR) in the 120 mg/m2 group was 88.9% (95% CI: 65.3-98.6).
With a median follow-up of 24 weeks, all confirmed responses in the 120 mg/m2 dose group were ongoing at the time of data cutoff. These results have led to the selection of Rina-S 120 mg/m2 for further evaluation in a Phase 3 trial, expected to commence in 2024, focusing on patients with advanced ovarian cancer.
Safety Profile
The Phase 1/2 study also provided insights into the safety profile of Rina-S. Common treatment-emergent adverse events (TEAEs) included anemia, neutropenia, nausea, thrombocytopenia, leukopenia, fatigue, vomiting, alopecia, and diarrhea. Dose reductions and treatment discontinuations were infrequent, and importantly, no signals of ocular toxicities, neuropathy, or interstitial lung disease (ILD) were observed.
Expert Commentary
"Ovarian cancer presents a significant challenge, especially for those with advanced or recurrent cases, where treatment options and prognosis are often limited," said Dr. Elizabeth Lee, a medical oncologist at Dana-Farber. "The encouraging Phase 1/2 data for Rina-S demonstrates the potential for future treatment options for patients. We are looking forward to additional data from tumor-specific dose expansion cohorts."
About Rinatabart Sesutecan
Rinatabart Sesutecan (Rina-S; GEN1184) is a clinical-stage, FRα-targeted, Topo1 ADC currently in Phase 2 development for ovarian cancer and other FRα-expressing solid tumors. In January 2024, the U.S. Food and Drug Administration granted Fast Track designation to Rina-S for treating patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.
Ovarian Cancer Landscape
Ovarian cancer is a significant global health concern, with over 320,000 new cases diagnosed annually worldwide. It is often diagnosed at an advanced stage due to non-specific symptoms. While platinum-based chemotherapy, often combined with targeted therapies and surgery, remains the standard treatment, recurrence rates are high, with approximately 70-90% of women with advanced-stage ovarian cancer experiencing recurrence. The five-year survival rate remains low, generally hovering around 30-50%.
