Design of Phase 2 study NeoFox, revision

Phase 2 study NeoFox with Foxy-5 will now include patients with stage III colorectal cancer, who are assessed to have a high risk of recurrence after the primary tumor has been surgically removed. This is done according to established assessment criteria.

The objective of the study is to demonstrate that Foxy-5 reduces the size of the tumor’s local spread in the colon in patients with colorectal cancer, i.e., the invasion of the primary tumor into the colon wall and lymph nodes decreases.

Patients are treated with Foxy-5 from the time of diagnosis, when they are included in the study, until the operation, which usually occurs within 4 weeks of diagnosis. After an additional month, the patient makes a final visit and concludes the study.

Foxy-5 has a very favorable side effect profile, without the problems that typically arise with conventional treatment.

Latest news about the study:

The redesigned NeoFox study is fully approved in both Spain and Hungary. The study begins by evaluating two higher doses than previously used in a limited number of patients. The first patient was recruited in October, and the initial dose group showed a consistently favorable side effect profile. The evaluation of the second, higher dose group is ongoing.

New study plan:

The new design consists of Part 1 and Part 2. In both parts, the treatment duration is the same: Foxy-5 dosing begins as before at the time of diagnosis and continues until the operation, when it is concluded, and the effect is evaluated. This means that patients are treated for at least 3 weeks.

Part 1 will evaluate how a more frequent dosing frequency in combination with higher doses than previously administered is tolerated by approximately 6 patients. This dose escalation is made possible by the very favorable side effect profile that Foxy-5 has shown in the NeoFox study.

Part 2 will evaluate the effect of the highest tolerated dose in Part 1 in approximately 80 patients. The new efficacy measures are based on ad hoc observations made in the original NeoFox design. In that study, a decreased TNM grading (downstaging according to the American Joint Committee on Cancer (AJCC) 8th edition 2017) of the primary tumor and regional lymph nodes was observed in the group receiving Foxy-5 compared to the control group (p=0.012).

The goal of the change is to demonstrate that Foxy-5 reduces the size of the tumor’s local spread in the colon in patients with stage III colorectal cancer, i.e., that the primary tumors and lymph nodes with tumor cells decrease in size and number. The changes will be studied radiologically using computed tomography (CT). The evaluation involves a comparison of the effect of Foxy-5 against a control group without Foxy-5 treatment.

In addition, a pathological examination of surgically removed tumors and lymph nodes will be conducted using microscopy. This will confirm, among other things, the previous observations of a reduced perineural invasion (i.e., fewer patients have spread along nerves, p=0.0088) and a reduced vascular invasion (i.e., fewer patients have spread around blood vessels, p=0.0097) after treatment with Foxy-5. Observations that may indicate a reduced risk of recurrence after surgery for patients.

Both the radiological and microscopic examinations will be evaluated by independent experts.

Patients in the original study plan:

The company assesses that the NeoFox study should not be completed as originally planned, as the study did not intend to study any parameters at the time of surgery. Recruitment to the study was paused last fall, and approval of the revised study plan means that the follow-up of the remaining patients from the original study design will be concluded.

Revised study plan for NeoFox provides time and cost savings:

Changes to the study plan result in significant cost and time savings. The number of treatment doses is significantly reduced, and the time to evaluate the first efficacy measures is shortened significantly, from 24 months to be able to occur immediately after surgery. We thus have a good opportunity to obtain a strong indication of the clinical effect of Foxy-5 earlier than originally planned, something that will be confirmed in subsequent studies, where we also intend to determine the drug’s complete effect on the occurrence of metastases and overall survival.