Abstract 9P
Background
Patients with normal or near normal expression of the WNT5A protein in their breast-, colon- or prostate primary cancers have a better overall survival and longer recurrence-free survival. To improve the prognosis for those patients that lack or have a low expression of the WNT5A protein, a small WNT5A mimicking peptide, Foxy-5, was developed. Pre-clinical in vitro and in vivo experiments revealed that Foxy-5 effectively impaired cancer cell invasion and metastasis. Further, Foxy-5 was assessed in two clinical phase 1 studies in patients with breast-, colon- and prostate cancer and considered to be safe and well tolerated.
Methods
A randomized, controlled, and open multicenter phase 2 clinical study in localized colon cancer, NeoFox, was initiated in Spain and Hungary. After a diagnosis of stage II/III colon cancer was confirmed by CT and biopsy, a three-doses per week neo-adjuvant treatment period with Foxy-5 was initiated with at least 9 intravenous administrations of the drug candidate. The Foxy-5 treatment was paused during surgery and was re-initiated with three-doses per week until start of chemotherapy. An ad hoc analysis of totally 110 patients was performed at the time of surgery.
Results
The pathological examination of primary tumours revealed that significantly fewer patients treated with Foxy-5 exhibited venous invasion of cancer cells (p=0.0097) as well as perineural invasion (p=0.0088). Furthermore, TNM downstaging (p=0.012) from time of preliminary diagnosis to time of surgery was more frequent in patients treated with Foxy-5. The results remain significant even when controlling for baseline factors such as age, sex and clinical site at inclusion in the study. These ad hoc observations indicate that patients treated with Foxy-5 may have a better outcome compared to patients in the control arm.
Conclusions
Our ad hoc observations show 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 patients 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.
Clinical trial identification
EudraCT 2018-003074-27.
Legal entity responsible for the study
WntResearch AB.
Funding
WntResearch.
Disclosure
R. Salazar Soler: Financial Interests, Personal, Advisory Board: GSK, Sanofi Genzyme; Financial Interests, Personal, Expert Testimony: Laboratorios Servier, Esteve; Financial Interests, Personal, Other, Commercial Medical Education Company owned by wife until December 2023: SACE Medhealth; Financial Interests, Personal, Other, Co-administrator and co-owner of this commercial medical education company until April 2022: SACE Medhealth; Financial Interests, Personal, Other, Member of executive committee: TTD; Financial Interests, Personal and Institutional, Invited Speaker: WNT Pharma. C. Santos Vivas: Financial Interests, Personal, Advisory Board: Sanofi, Amgen, Pierre Fabre; Financial Interests, Personal, Other, Travel and accommodation: Merck KGaA, Merck. A. Yubero Esteban: Financial Interests, Personal, Advisory Board: Clovis Oncology, AstraZeneca, GSK, PharmaMar; Financial Interests, Institutional, Invited Speaker: WntResearch AB. J. Gallego Plazas: Financial Interests, Personal, Advisory Board: AAA, Amgen, Bayer, BMS, Eisai, Ipsen, Lilly, Merck, MSD, Pierre Fabre, Roche, Servier; Financial Interests, Personal, Invited Speaker: AAA, Amgen, Bayer, BMS, Ipsen, Lilly, Merck, MSD, Novartis, Servier; Financial Interests, Personal, Other, Educational: Amgen, Ipsen, Merck, Novartis, Pierre Fabre, Roche; Financial Interests, Institutional, Funding: Astellas, AstraZeneca, BMS, Daiichi Sankyo, Lilly, Servier; Non-Financial Interests, Member of Board of Directors: Spanish Society Medical Oncology, Spanish Group of Neuroendocrine an Endocrine Tumours; Non-Financial Interests, Project Lead: AGAMENON-SEOM Registry of Esophagogastric Cancer. A. Cervantes: Financial Interests, Institutional, Advisory Board: Merck Serono, Amgen, Roche, Transgene, AnHeart Therapeutics, AbbVie, GSK; Financial Interests, Institutional, Invited Speaker: Amgen, Roche, Merck Serono, Foundation Medicine; Financial Interests, Personal, Other, Associate Editor: Annals of Oncology, ESMO Open; Financial Interests, Personal, Other, Editor in Chief: Cancer Treatment Reviews; Financial Interests, Institutional, Research Grant, Principal Investigator: Actuate Therapeutic, Amgen, Astellas Pharma, BeiGene, Bayer, AstraZeneca, BMS, Amcure, FibroGen, Lilly, Genentech, MedImmune, Merck Serono, Novartis, Natera, MSD, Servier, Sierra Oncology, Adaptimmune, Takeda, Affimed, Roche, Seamless, Gilead, Janssen, F-star Therapeutics, Ribon Therapeutics; Non-Financial Interests, Other, Scientific Director: INCLIVA Biomedical Research Institute. P. García Alfonso: Financial Interests, Personal, Advisory Board: Amgen. D. Paez: Financial Interests, Personal, Invited Speaker: MSD, Novartis, BMS; Financial Interests, Personal, Advisory Board: Amgen, Esteve, Ipsen; Financial Interests, Personal and Institutional, Research Grant: Merck. A. Ruiz-Casado: Financial Interests, Personal, Invited Speaker: Servier, Abbott, Nestle, Medtronic; Financial Interests, Personal, Advisory Board: Pierre Fabre, Amgen. C. Lopez: Financial Interests, Personal, Invited Speaker: Ipsen, Roche, Eisai, Novartis, Pfizer, AAA, Bayer, Lilly, Amgen, Merck, AstraZeneca, Servier, Ipsen, Ipsen, Roche, Ipsen, Eisai; Financial Interests, Personal, Advisory Board: Ipsen, Roche, Eisai, Pfizer, Bayer, Lilly, Amgen, Merck, AstraZeneca, Servier; Financial Interests, Personal, Funding: Roche, Pfizer, Novartis, Bayer, Lilly, Eisai; Financial Interests, Personal and Institutional, Research Grant: Amgen, AstraZeneca, Servier. A. Furka: Financial Interests, Personal, Invited Speaker: Pfizer, MSD, Krka, Bayer, AstraZeneca, Sanofi; Financial Interests, Personal, Advisory Board: Krka; Financial Interests, Personal and Institutional, Invited Speaker: Wntresearch, AstraZeneca, MSD; Non-Financial Interests, Member of Board of Directors: Hungarian Society of Clinical Oncology. All other authors have declared no conflicts of interest.