Isofol Medical has initiated the assessment of results from the Phase III AGENT clinical trial of its drug candidate, arfolitixorin, plus 5-FU, oxaliplatin and bevacizumab to treat advanced, metastatic colorectal cancer (mCRC).
The read-out process began after holding talks with the US Food and Drug Administration (FDA) on the censoring rules and the number of progression-free survival (PFS) events needed to commence the data collection and assessment.
Isofol will decide on the number of PFS events for cut-off, which the regulatory agency will take into consideration during the review of the New Drug Application (NDA).
Arfolitixorin is in the developmental stage to boost the efficacy of standard of care chemotherapy for advanced colorectal cancer.
The multicentre, global, randomised, controlled trial will analyse the safety and efficacy of arfolitixorin, [6R]-5,10-methylene-THF acid (MTHF) versus leucovorin, both used along with 5-FU, oxaliplatin, and bevacizumab, in patients with first-line metastatic colorectal cancer.
Subjects in the trial will be divided into a 1:1 ratio to receive the treatment.
The trial is underway at nearly 90 sites in the US, Canada, Australia, Japan and Europe.
Overall response rate (ORR) is the trial’s primary endpoint while PFS and duration of response (DOR) will be analysed as key secondary endpoints.
Furthermore, overall survival (OS), number of curative metastasis resections, safety and subjects reported outcomes such as quality of life (QoL) will be included as the trial’s other secondary endpoints.
Exploratory endpoints comprise pharmacokinetic (PK) assessments and gene expression levels of folate relevant genes in tumour cells.
The trial is intended to demonstrate the superiority of arfolitixorin over leucovorin.
A thorough review of possibilities for an updated SAP resulted in new considerations for assessing the data, Isofol noted.
The company plans to submit the assessments of the trial based on 490 subjects as well as both the original and updated censoring rules in the NDA.
Isofol Medical CEO Ulf Jungnelius said: “There is a profound unmet need in metastatic colorectal cancer, yet few therapies are being studied to benefit the majority of patients versus specific targets.
“At Isofol, we have been singularly focused on identifying a simple and more effective modernisation of the standard of care to further reduce the tumour burden and increase life span for more patients.”
In May last year, the company completed enrolment of Japanese participants in AGENT trial of arfolitixorin in first-line mCRC patients.