ONGOING PHASE 2 STUDY NEOFOX
The company is currently conducting the NeoFox Phase 2 study with Foxy-5. NeoFox is an open-label study, i.e. the study data is available during the course of the study but interpretation requires certain data volumes to be scientifically validated.
The study is currently ongoing in around 25 hospitals in Spain and Hungary and started in 2019. It has been delayed due to the Covid-19 pandemic when treating hospitals re-prioritised their resources while covid restrictions complicated patients’ treatment and testing schedules.
NeoFox includes patients with stage II/III colon cancer who, at diagnosis, are considered to be at high risk of recurrence after surgery to remove the primary tumour. This is done according to established assessment criteria. The goal of the study was initially, prior to the unexpected observations communicated by the Company in August and confirmed in October, to demonstrate that Foxy-5 reduces the risk of disease relapse within two years, primarily in patients with low expression of WNT5A.
To optimise the prevention of tumour spread, the original study design was to initiate treatment with Foxy-5 at the time of preliminary diagnosis. The ambition was to provide at least 9 treatments with Foxy-5 before surgery. The patient is normally undergoing surgery within 4 weeks of diagnosis and the Foxy-5 treatment continues after surgery until chemotherapy is started (normally 1-2 months after surgery) or until the patient has received a maximum of 39 treatments with Foxy-5. The primary evaluation in NeoFox was and is a comparison of the effect of Foxy-5 against a control group without Foxy-5 treatment.
The statistical analysis of the study’s primary and secondary endpoints is described in a statistical analysis plan, which is always produced for a clinical trial.
Patients are currently being followed for a total of 24 months, given that the majority of all relapses typically occur within 12-24 months of diagnosis. The risk of and time to relapse is evaluated using overall survival (OS) and disease-free survival (DFS) endpoints. The surrogate marker ctDNA (circulating tumour DNA) is analysed in the blood of all patients enrolled in the study. ctDNA is a new technique that is expected to provide an early signal for relapse. Measuring ctDNA can indicate that the disease is recurring before visible metastases can be detected by traditional X-rays or blood tests.
UNEXPECTED AND CONFIRMED OBSERVATIONS
At the time of the Company’s press release on 16 August, it was decided that NeoFox should not be completed as originally planned as the Company had not anticipated the rapid effects observed. Therefore, the Company decided to pause further recruitment of patients into the study while treatment and follow-up of the already 127 included patients has continued as planned. Following extended analysis of pathology reports from a total of 118 patients included in NeoFox, reduced tumour burden (in primary tumour and regional lymph nodes), so-called down staging, as well as reduced spread along the nerves (perineural invasion) can be confirmed. In addition, the expanded study material shows a confirmed reduction in spread to blood vessels (vascular invasion). The unexpected observations showed an effect already after three weeks of treatment before surgery. These effects were not optimally studied in the original study design.
UPDATE OF EFFICACY MEASURES
Considering the confirmed observations, an addition to the NeoFox study design is now being made to validate these. The observed parameters are planned to be included as new efficacy measures in the revised study design. The advantage is that these can be evaluated already at surgery after about three weeks of pre-surgical treatment with Foxy-5. According to the original study plan, the current endpoints would only be derived two years after surgery.
PREVIOUSLY PLANNED INTERIM ANALYSIS NOT CARRIED OUT
The change in efficacy measures means that the previously planned interim analysis, which would have guided the decision on the total number of patients in NeoFox, will not be carried out. The number of patients needed going forward is estimated to be around 200 patients in total (which will include the 127 patients already enrolled), which is about the same as the NeoFox study was originally planned for.
ONGOING STUDY MODIFICATION
The revising of the study plan is now underway and it will be submitted for approval by the pharmaceutical authorities and ethics review boards where the study is being conducted. Following approval, patient recruitment will resume, which is expected to occur in spring 2023. The paused patient recruitment for the study will thus continue in the meantime, while treatment and follow-up of already included patients will continue as planned.
The revised study plan is expected to allow WntResearch to consolidate proof of concept in humans in a shorter timeframe compared to before. In addition, previously generated data from the NeoFox study can be used, which contributes to time and cost efficiency.