Ascendis Pharma A/S (Nasdaq: ASND) has announced initial data from its Phase 1/2 IL-Believe Trial, revealing promising anti-tumor activity of TransCon IL-2 β/γ in patients with platinum-resistant ovarian cancer (PROC). The study, presented at the ESMO 2024 meeting in Barcelona, demonstrated clinical responses in heavily pre-treated PROC patients, offering a potential new treatment option for those who have exhausted standard-of-care therapies.
Promising Clinical Responses in Heavily Pre-treated Patients
The IL-Believe trial evaluated TransCon IL-2 β/γ in combination with chemotherapy in PROC patients. Initial data from 18 patients (median age 64 years) showed that 14 were efficacy-evaluable. The results indicated that 29% (4/14) of these patients experienced anti-tumor clinical responses. Notably, the patient population included individuals who had previously progressed on Elahere, also known as mirvetuximab soravtansine-gynx, suggesting the potential for TransCon IL-2 β/γ to overcome resistance to existing treatments.
Safety and Tolerability
The combination therapy was generally well-tolerated. The most common treatment-emergent adverse events (TEAEs) related to the combination of TransCon IL-2 β/γ plus chemotherapy included fatigue, thrombocytopenia, neutropenia, and anemia. The majority of TransCon IL-2 β/γ-related TEAEs were grade 1 or 2, indicating manageable side effects.
Mechanism of Action and Trial Design
TransCon IL-2 β/γ is a novel prodrug designed for sustained release of an IL-2Rβ/γ-selective IL-2 analogue (IL-2 β/γ). The TransCon linker technology allows for a predictable and sustained release of active IL-2 β/γ, resulting in lower Cmax and a longer half-life, potentially widening the therapeutic index. The IL-Believe trial is a multicenter Phase 1/2 study involving adult patients with locally advanced or metastatic solid tumors. The PROC dose expansion cohort (Cohort 3) included patients whose disease had progressed within six months after completing platinum-based chemotherapy. These patients received intravenous TransCon IL-2 β/γ at a dose of 120 μg/kg every three weeks, combined with physician's choice of paclitaxel, docetaxel, or pemetrexed. Disease response was assessed every nine weeks using RECIST v1.1 criteria.
Expert Commentary
Stina Singel, M.D., Ph.D., Executive Vice President, Head of Clinical Development, Oncology, at Ascendis Pharma, stated, "Building on results announced at ASCO 2024 in melanoma, we are excited now to see meaningful signs of anti-tumor activity in combination with chemotherapy in our second indication-specific cohort of heavily pretreated patients who have exhausted standard-of-care options. We look forward to providing further updates as patients continue on study treatment."
Future Outlook
While these initial results are encouraging, further data on durability of response and overall survival are needed to fully assess the clinical benefit of TransCon IL-2 β/γ in PROC. Ascendis Pharma plans to provide additional updates as the trial progresses.
