Ascendis to Present Initial PROC Phase 1/2 IL-Believe Trial Results at ESMO 2024

Initial data from Ascendis Pharma A/S's Phase 1/2 IL-Believe Trial reveals promising clinical activity in patients with heavily pre-treated platinum-resistant ovarian cancer (PROC). These patients have been treated with TransCon IL-2 β/γ in combination with chemotherapy. The data was presented at ESMO 2024 in Barcelona.

In this trial, 18 patients with a median age of 64 years were included. Fourteen of these patients were deemed efficacy evaluable, having undergone at least one post-baseline tumor assessment. Additionally, four patients discontinued treatment prior to their first post-baseline assessment due to disease progression or death. Among the 14 efficacy-evaluable patients, anti-tumor responses were observed in 29% (four patients). These responses included two confirmed and two unconfirmed partial responses. Some patients had previously been treated with Elahere® (mirvetuximab soravtansine-gynx), and had seen disease progression. This suggests that TransCon IL-2 β/γ may offer clinical benefits even in heavily pre-treated patients.

The combination therapy was generally well-tolerated. The most common treatment-emergent adverse events included fatigue, thrombocytopenia, neutropenia, and anemia. Most adverse events associated with TransCon IL-2 β/γ were mild or moderate in severity.

Stina Singel, Executive Vice President and Head of Clinical Development, Oncology at Ascendis Pharma, expressed enthusiasm about the results. She highlighted that the findings build on earlier results from a similar study in melanoma, showing significant anti-tumor activity in patients who have exhausted standard treatment options. She indicated that further updates would be provided as the study progresses.

TransCon IL-2 β/γ is a novel prodrug designed for sustained release of an IL-2Rβ/γ-selective IL-2 analogue. This analogue is attached to an inert carrier via a TransCon linker, which enables predictable and sustained release of active IL-2 β/γ under physiological conditions. This mechanism aims to achieve a lower maximum concentration (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. As of the data cut-off on July 29, 2024, the trial enrolled 42 patients with PROC who had disease progression within six months after completing platinum-based chemotherapy. Patients in the PROC dose expansion cohort received intravenous TransCon IL-2 β/γ at a recommended Phase 2 dose of 120 μg/kg every three weeks, combined with the physician’s choice of paclitaxel, docetaxel, or pemetrexed. Disease response assessments were conducted every nine weeks using RECIST v1.1 criteria. Safety, efficacy, and biomarkers were also evaluated.

Ascendis Pharma aims to leverage its innovative TransCon technology platform to become a leading biopharma company. The company's focus is on creating therapies that make a meaningful difference in patients' lives. Ascendis Pharma is headquartered in Copenhagen, Denmark, with additional facilities in Europe and the United States.