The AGENT study (Phase III)

The AGENT study

The AGENT study is a randomized, controlled, multi-centre study assessing the efficacy and safety of arfolitixorin, [6R]-5,10-methylene-THF acid (MTHF), compared to leucovorin, both used in combination with 5- FU, oxaliplatin, and bevacizumab, in first line metastatic colorectal cancer patients. Patients are randomized in a 1:1 ratio.

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.

Treatment arms

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.

Interim 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. The independent Data Safety and Monitoring Board (iDSMB) has evaluated safety and efficacy (ORR and PFS). iDSMB has recommended Isofol to continuation the AGENT study with 440 patients, in accordance with the study design for arfolitixorin. Isofol remains blinded to the interim analysis results.

Final analysis

In December 2020, the last of the AGENT study’s 440 patients was recruited, which was the basis for the statistical analysis plan approved by the FDA and EMA. Isofol is now focusing on completing the ongoing AGENT study in which 440 patients receive first-line standard treatment for metastatic colorectal cancer (mCRC). The company expects that the final results of the AGENT study will be available during H1 2022.