Genmab A/S has announced promising results from its Phase 1/2 study of rinatabart sesutecan (Rina-S), an investigational antibody-drug conjugate (ADC) targeting folate receptor-alpha (FRα) for the treatment of ovarian cancer. The study revealed a 50% confirmed objective response rate (ORR) in heavily pretreated patients treated with Rina-S at 120 mg/m2 every three weeks, irrespective of FRα expression levels.
The Phase 1/2 trial randomized 42 previously treated patients with advanced ovarian cancer to either Rina-S 100 mg/m2 (n=22) or Rina-S 120 mg/m2 (n=20). Ninety-five percent of patients in the 120 mg/m2 group had platinum-resistant ovarian cancer, as did 90.9% of patients in the 100 mg/m2 group. The confirmed ORR was 18.2% in the 100 mg/m2 group, compared to 50.0% in the 120 mg/m2 group. The disease control rate (DCR) was 86.4% and 88.9% for the 100 mg/m2 and 120 mg/m2 groups, respectively. With a median follow-up of 24 weeks, all confirmed responses in the 120 mg/m2 group were ongoing at the data cutoff.
Clinical Implications
These results suggest that Rina-S could offer a valuable treatment option for patients with advanced or recurrent ovarian cancer, where treatment options are limited. The 50% ORR observed in platinum-resistant ovarian cancer patients is particularly encouraging. According to Elizabeth Lee, MD, a medical oncologist at Dana-Farber, the data demonstrates the potential for future treatment options for patients.
Safety and Tolerability
In the Phase 1/2 study, common treatment-emergent adverse events (TEAEs) included anemia, neutropenia, nausea, thrombocytopenia, leukopenia, fatigue, vomiting, alopecia, and diarrhea. Dose reductions and treatment discontinuations were infrequent. Notably, no signals of ocular toxicities, neuropathy, or interstitial lung disease (ILD) were observed.
Future Development
Based on these findings, Rina-S at 120 mg/m2 has been selected for further evaluation in a Phase 3 trial for patients with advanced ovarian cancer, expected to commence in 2024. This trial will assess the efficacy and safety of Rina-S in a larger patient population.
Mechanism of Action
Rinatabart Sesutecan (Rina-S; GEN1184) is a clinical-stage, FRα-targeted, Topo1 ADC, currently in Phase 2 development for the treatment of 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 the treatment of 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. Platinum-based chemotherapy, combined with targeted therapies and surgery, remains the standard treatment. However, approximately 70-90% of women with advanced-stage ovarian cancer experience recurrence after initial treatment. The five-year survival rate remains low, varying between 30-50% depending on the region.
