The AGENT study
Isofol is now focused on finalizing the ongoing global Phase III AGENT study (ISO-CC-007) where 440 patients receives first line standard treatment for metastatic colorectal cancer (mCRC). In total, approximately 90 hospitals are participating in the USA, Canada, Europe, Australia and Japan. In July 2020, 330 patients had 330 patients had been recruited into the study, which opening up for the interim analysis and in December 2020, the AGENT study reached 440 patients, which was the basis of the statistical analysis plan approved by the FDA and EMA.
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.
The statistically significant is to show an improvement in tumor shrinkage in the patients treated with arfolitixorin compared to those treated with leukovorin by at least 10 percentage points. At the same time, we at least want to see a positive trend in progression-free survival.
Interim analysis and final analysis
The interim analysis is based on 330 patients and was initiated when the 330th patient had been treated for 16 weeks and had two tumor evaluations. Data is now being reviewed and quality controlled, once that has been done an independent group, Data Safety Monitoring Board (iDSMB) will evaluate safety and efficacy (ORR and trend in PFS). 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, iDSMB may propose an extension of the study with another 220 patients (in addition to the 440 patients) to increase the statistical power for evaluation of PFS. The result from the analysis is expected during the first quarter of 2021.
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.