Doctor discussing treatment options with a patient.
Doctor discussing treatment options with a patient.

The open-label extension Phase I/IIa clinical trial, ISO-CC-005, investigates arfolitixorin (Modufolin; MTHF; Isofol Medical) as part of the first-line treatment regimen in patients with metastatic colorectal cancer (mCRC) eligible for 5-FU/folate therapy alone or in combination with irinotecan or oxaliplatin ? bevacizumab.

Arfolitixorin is an investigational candidate being developed to increase the efficacy of standard of care chemotherapy for advanced colorectal cancer. One of the unique benefits of the trial drug is that, as the key active metabolite of the widely used folate-based drugs, arfolitixorin can potentially benefit all patients with advanced colorectal cancer, as it does not require complicated metabolic activation to become effective.

Initial results

Recently published results confirm preliminary response assessment data from 19 patients treated for 8-32 weeks. These results showed a best overall response rate (ORR) in 58% of patients (11/19). The participating patients were treated with the selected dose regimen of 120 mg/m? arfolitixorin and 5-fluorouracil (5-FU) with either irinotecan or oxaliplatin (ARFIRI/ARFOX).* Best ORR is defined as a greater than 30 % reduction in tumor size from baseline.

Earlier reports

“Earlier this year we reported clinical data after 8 weeks from this patient population showing promising results with early tumor shrinkage, defined as a greater than 20% reduction in tumor size, in 47 % of patients. After following these patients for up to 32 weeks, preliminary best overall response rate (ORR) demonstrates that 58% of patients now had a greater than 30% reduction in tumor size from baseline,” noted Roger Tell, M.D.,Ph.D., Chief Scientific Officer of Isofol Medical.

“We are excited to continue to explore this endpoint with our ongoing global pivotal Phase III AGENT study as well as in the ongoing extension cohorts of the ISO-CC-005 study,” Tell added.

Trial design

The ISO-CC-005 is a dose finding study which evaluated four different ascending doses of arfolitixorin in combination with 5-FU, oxaliplatin or irinotecan and bevacizumab in patients with metastatic colorectal cancer (mCRC).

The study dose of arfolitixorin was determined to 120 mg/m?. The first extension arm with an additional 20 patients** was designed to further evaluate the safety and efficacy of the selected dose regimen of arfolitixorin in combination treatment with 5-FU and oxaliplatin or irinotecan. A second extension arm of an additional 20 patients are currently undergoing treatment and preliminary 8-week early tumor shrinkage data is expected mid-2019 and follow-up data for best response of ORR expected at year end 2019.

“The promising results announced today are in line with the targeted best ORR for our global pivotal Phase III AGENT study with arfolitixorin and are above the established ORR for standard of care, FOLFOX therapy, for advanced colorectal cancer, which is typically in the 40-45 % range,” explained Karin Ganl?v, M.D., Chief Medical Officer of Isofol Medical.

“We are encouraged by these results which further support the potential of arfolitixorin benefiting patients with metastatic colorectal cancer,? she added.

Global trial

In December 2018, Isofol announced that the first patient was enrolled in the global pivotal Phase III AGENT clinical study with arfolitixorin in mCRC (ISO-CC-007, NCT03750786). This trial is a multicenter, randomized, controlled study with blinded independent review of tumor response. Top-line data from the study is expected in 2021.[1]

Notes

*After the initial 8 weeks treatment 8 patients out of 19 also received bevacizumab which is coherent with the selected dose regimen in Isofol?s ongoing pivotal Phase III AGENT clinical study with arfolitixorin in mCRC.

**One patient was not included in the data analysis after dropping out of treatment during the study.

Reference

[1] Garcia D. Phase III AGENT Trial Enrolls First Metastatic Colorectal Cancer Patient. OncoZine, December 19, 2018 [Article]