KEY TAKEAWAYS
- The NeoFox phase II trial aimed to assess the feasibility and efficacy of a neo-adjuvant treatment regimen in pts with stage II/III colon cancer.
- The Ad hoc observations suggested Foxy-5 impairs invasion and induces downstaging in stage II/III colon cancer.
Patients (pts) with normal or near normal WNT5A expression in their breast cancer, colon cancer- or prostate primary cancers have better overall survival (OS) and longer recurrence-free survival (RFS). Foxy-5 – a small WNT5A-mimicking peptide was developed to improve the prognosis for pts with a low or lacking expression of WNT5A protein.
Preclinical experiments (both in vitro and in vivo) demonstrated that Foxy-5 showed efficacy in impairing the metastasis and cancer cell invasion. Furthermore, Foxy-5 was evaluated in two phase 1 clinical studies that involved pts with breast, colon, and prostate cancer and found safe and well-tolerated.
Ramón Salazar and the team designed this study to evaluate the feasibility and efficacy of a neo-adjuvant treatment regimen with Foxy-5 in pts with stage II/III colon cancer.
This randomized, controlled, and open multicenter phase 2 clinical study, NeoFox, was initiated in Spain and Hungary. After the diagnosis of stage II/III colon cancer was confirmed by CT and biopsy, a three-dose per week neo-adjuvant treatment period with Foxy-5 was initiated, with at least nine intravenous administrations of the drug candidate. The Foxy-5 treatment was paused during surgery and was re-initiated with 3 doses per week until the start of chemotherapy. An ad hoc analysis was performed on 110 pts, at the time of surgery.
Results indicated that the pathological examination of primary tumors revealed significantly fewer pts treated with Foxy-5 exhibited venous invasion of cancer cells (P=0.0097) and perineural invasion (P=0.0088). Furthermore, TNM downstaging (P=0.012) from the time of preliminary diagnosis to the time of surgery was more frequent in pts treated with Foxy-5.
These results remained significant even when controlling for baseline factors such as age, sex, and clinical site at inclusion in the study. These ad hoc observations suggested that pts treated with Foxy-5 may had a better outcome vs pts in the control arm.
The ad hoc observations concluded that neo-adjuvant treatment with the drug candidate Foxy-5 may impair both venous and perineural invasion and may also induce TNM downstaging when administered pre-operatively in pts with stage II/III colon cancer. Based on these retrospective analyses, the NeoFox study will be amended to confirm the observations in a prospective setting.
The trial was funded by WntResearch.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/3
Clinical Trial: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003074-27
Salazar R, Vivas C S, Macias I, et al. (2024). “Positive ad hoc results from neoadjuvant Foxy-5 treatment of colon cancer patients in the ongoing phase II NeoFox study.” Presented at ESMO-GI 2024, (Abstract 9P).
