A first patient has been enrolled in the pivotal Phase III AGENT clinical study designed to evaluate arfolitixorin (Modufolin®; Isofol Medical) for the treatment of metastatic colorectal cancer (mCRC).
The AGENT trial (NCT03750786) is a randomized, controlled, multi-center study with blinded independent review of the tumor response and is expected to enroll approximately 440 mCRC patients, who are at least 18 years or older, to receive arfolitixorin or leucovorin, both in combination with 5-fluorouracil (5-FU), oxaliplatin, and bevacizumab according to modified FOLFOX-6. 
Patients participating in the trial will be randomized in a 1:1 ratio.
The study’s primary endpoint is Overall Response Rate (ORR) and the key secondary endpoints are Progression Free Survival (PFS) and Duration Of Response (DOR).
Other secondary endpoints include Overall Survival (OS), number of curative metastasis resections, safety, and patient reported outcomes such as health related Quality of Life (hrQoL).
Exploratory endpoints include pharmacokinetic (PK) measurements and level of gene expression of folate relevant genes in tumor cells.
Top-line data from the study is expected 2021.
Unmet medical need
Colorectal cancer is one of the most common forms of cancer with more than 1.8 million new cases identified globally every year. It has a high mortality rate and no new therapeutic options in more than a decade. The current standard of care, 5-Fluorouracil (5-FU) in combination with folates, only benefits a minority of CRC patients.
Due to a lack of new therapeutic options and a high mortality rate, CRC is a disease with a significant unmet need for effective new treatments.
Results from the Phase IIa dose escalation study with arfolitixorin (ISO-CC-005) demonstrated that show that 50% of patients (6/12) had partial response to arfolitixorin + FOLFOX treatment and 100% (5/5) patients at the highest dose had a partial response (based on overall response rate).
Withe the development of arfolitixorin Isofol Medical, the sponsor of the trial, is focusing on improving the efficacy of standard chemotherapy for advanced colorectal cancer. This could potentially benefit all patients with advanced CRC.
“The enrolment of the first patient in the AGENT study… is the most important achievement in accelerating the development of arfolitixorin towards a market registration,” said Anders Rabbe, CEO of Isofol Medical.
“We are now looking forward to quickly ramp up enrolment to meet the interest from participating hospitals and physicians. Arfolitixorin, which has shown promising efficacy and good safety, is an important new treatment option for patients since few new therapeutic agents have been introduced in 1st line treatment of mCRC the last decade,” commented Karin Ganlöv, MD, Chief Medical Officer, Isofol Medical
The first patient was enrolled by Pratibha Desai MD, MPH, at Pinellas Hematology Oncology Clinic in Saint Petersburg, Florida, one of the approximately 80 sites in the US, Canada and western Europe where the trial is being conducted.
 A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer (AGENT) – [NCT03750786]
 Modufolin® in Combination With 5-Fluorouracil Alone or Together With Oxaliplatin or Irinotecan in Colorectal Cancer – [NCT02244632]
Last editorial review: December 19, 2018
Featured Image: Clinical trial Concept Courtesy: 2018 © Fotolia. Used with permission. Photo 1.0 and Photo 1.0 Courtesy: 2018 Isofol Medical AB.
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