Rina-S Shows Promising Anti-Tumor Activity in Phase 1/2 Trial for Ovarian and Endometrial Cancers

New Data on Rina-S Demonstrates Promising Results in Ovarian Cancer Treatment

In a recent announcement, Genmab A/S shared encouraging findings from its Phase 1/2 clinical study of rinatabart sesutecan (Rina-S), an experimental antibody-drug conjugate targeting folate receptor-alpha (FRα). The study revealed a notable objective response rate (ORR) of 50.0% among heavily pretreated ovarian cancer patients receiving Rina-S at a dose of 120 mg/m2 every three weeks, independent of their FRα expression levels. These promising results were presented at the 2024 European Society of Medical Oncology Congress held in Barcelona, Spain.

The study's Part B phase involved 42 patients with advanced ovarian cancer who had previously undergone treatment. These patients were randomly assigned to receive either 100 mg/m2 or 120 mg/m2 of Rina-S. In the 120 mg/m2 group, which consisted of 20 patients, 95% were classified as having platinum-resistant ovarian cancer (PROC). Among the 22 patients in the 100 mg/m2 group, 90.9% were also determined to be PROC.

The study’s results for the 100 mg/m2 and 120 mg/m2 doses were as follows: the ORR was 18.2% for the 100 mg/m2 group compared to 50.0% for the 120 mg/m2 group. Specific outcomes in the 100 mg/m2 and 120 mg/m2 groups included a complete response in 0% and 5.6% of patients, partial responses in 18.2% and 44.4%, stable disease in 68.2% and 38.9%, and disease progression in 13.6% and 5.6%, respectively. Only one patient in the higher dose group was not evaluable. Importantly, at a median follow-up of 24 weeks, all responses in the 120 mg/m2 group were still ongoing.

The disease control rates (DCR) for the 100 mg/m2 and 120 mg/m2 groups were 86.4% and 88.9%, respectively. Based on these compelling outcomes, the 120 mg/m2 dose of Rina-S will progress to a Phase 3 trial for advanced ovarian cancer patients, expected to commence in 2024.

Dr. Elizabeth Lee, a medical oncologist at Dana-Farber Cancer Institute, commented on the findings, stating, "Ovarian cancer poses a significant challenge, particularly for advanced or recurrent cases. The Phase 1/2 data for Rina-S holds promise for future treatment options. We eagerly anticipate further data from the ongoing dose expansion cohorts."

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 rare. Notably, there were no reports of ocular toxicities, neuropathy, or interstitial lung disease (ILD).

Jan van de Winkel, Ph.D., President and CEO of Genmab, expressed optimism about the trial results, stating, “The data from this ongoing trial suggest that Rina-S could offer significant anti-tumor activity beyond first-generation FRα-based therapies. We are committed to exploring the full potential of Rina-S in treating ovarian, endometrial, and other solid tumor cancers.”

This open-label, multicenter Phase 1/2 study evaluated the safety and efficacy of Rina-S at various doses in solid tumors expressing FRα. The study included several parts: dose-escalation cohorts, tumor-specific monotherapy dose-expansion cohorts, a platinum-resistant ovarian cancer cohort, and combination therapy cohorts.

In Part A, which involved dose escalation in patients with advanced solid tumors, including ovarian and endometrial cancers, the ORR was 30.8%, with partial responses in 30.8% of patients and stable disease in 57.7%. The DCR was 88.5%, and the median Duration of Response (DOR) was 35.3 weeks.

Part B included a dose expansion study in patients with advanced ovarian cancer, randomizing them to 100 mg/m2 or 120 mg/m2 dose groups. Most patients were heavily pretreated with a median of three prior lines of therapy, including bevacizumab, PARP inhibitors, and mirvetuximab soravtansin. Responses were observed across varying levels of FRα expression.

Ovarian cancer remains a significant global health issue, with over 320,000 new cases annually. It is often diagnosed at an advanced stage due to its non-specific symptoms, and it has a high recurrence rate after initial treatment. The five-year survival rate is generally low, ranging from 30-50%.

Rinatabart Sesutecan (Rina-S) is in Phase 2 development for treating ovarian cancer and other FRα-expressing tumors. It received Fast Track designation from the U.S. FDA for treating high-grade serous or endometrioid platinum-resistant ovarian cancer.