The AGENT study
Isofol is now focused on the initiated Pivotal Phase 3 AGENT study (ISO-CC-007) which is currently recruiting patients in the USA, Canada and Europe. In total around 80 hospitals will participate in recruiting around 440 patients who will receive first line treatment for metastatic colorectal cancer (mCRC).
The study will have two treatment arms: the first group will be treated with arfolitixorin, and the second, with leucovorin (today’s folate-based treatment), both in combination with the 5-FU and oxaliplatin chemotherapeutic agents and the biological therapy, bevacizumab (Avastin), see illustration below.
The primary focus of the study will be to measure the percentage of patients who experience tumour size reduction, (Objective Response Rate, ORR). The secondary endpoint will be the measurement of Progression Free Survival (PFS), i.e. the time until the tumour begins to grow again or the patient dies. A ststistically significant tumour shrinkage in 55-60 % of patients should be demonstrated. Isofol’s objective is, therefore, to achieve a 10-15% improvement in ORR in those patients treated with arfolitixorin in comparison with those treated with leucovorin.
Interim analysis and final analysis
An interim analysis of ORR and PFS will be performed after 330 patients have been treated for at least 16 weeks. With a positive outcome for tumor reduction, ORR (an improvement of about 10 percentage points) in the interim analysis combined with a positive trend for survival, PFS, an independent group, a so-called Data Safety Monitoring Board (DSMB), may propose an extension of the study with another 220 patients (a total of 660 patients) to strengthen the statistical basis for evaluation of PFS. The interim analysis is now planned for the first half of 2020, but is dependent on the outcome of the patient recruitment. The entire study is expected to be completed during the first half of 2021 (at 440 patients) or at the end of 2021 (at 660 patients).