Evaluation of Efficacy of Trifluridine/Tipiracil Plus an Anti-IL-1α True Human Antibody Versus Trifluridine/Tipiracil Plus Placebo in Metastatic Colorectal Cancer Patients After Failure of Oxaliplatin, Irinotecan, Fluoropyrimidine

Other concurrent malignancies the last 3 years, except adequately treated cone-biopsied in situ carcinoma (as per exemple of the cervix, basal cell, squamous cell carcinoma of the skin, low risk prostate cancer or other insitu carcinoma juged eligible according the coordinator). Patient who have had potentially curative therapy for a prior malignancy are eligible provided there has been no evidence of disease for ≥ 3 years and the risk of recurrence is considered low.

Symptomatic brain metastases

Estimated prognosis \<3 months.

Mutational status BRAF mutant (V600E only)

Participation in progress, or in the 30 days preceding the first scheduled day of dosing in this study, in another therapeutic trial with an experimental molecule or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer.

Severe unbalanced illness, underlying infection that may prevent the patient from receiving treatment. Patients with a clinically important and unresolved Grade 3 or 4 non-haematologic adverse reaction related to previous therapies. Also participant with any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.

Bowel obstruction or sub-obstruction or a history of inflammatory bowel disease or significant gasto intestinal disorder

History of autoimmune or inflammatory disease or interstitial lung disease.

Patient with congenital galactosemia, total lactase deficiency (lactose intolerance) or glucose-galactose malabsorption syndrome

Severe arterial thromboembolic events less than 6 months before randomization

New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg)

Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration.

-Contraindication to receive a treatment with trifluridine/tipiracil or an anti-IL-1α (XB2001 True Human antibody) and/or patient already treated by trifluridine/tipiracil, or an anti-IL-1α.

Concomitant systemic treatment with immunotherapy, immunosuppressants, corticosteroid therapy ≥ 10 mg equivalent prednisone/prednisolone or hormone therapy: corticosteroid therapy administered chronically, immunosuppressive treatment, biotherapy administered as part of the management of an inflammatory disease (anti-TNF, anti-IL6, anti-IL1, anti PD-1, anti EGFR etc.) and live virus vaccines administered up to 14 days prior the first scheduled dose of treatement administration.

Current pregnancy (mandatory pregnancy test at baseline for female of childbearing potential) or breastfeeding.

Patient with any psychiatric, psychological, sociological, geographical problem or other severe concomitant disease, disorder or condition that potentially compromising the understanding of the information, the safety of the patient, the interpretation of study results or the conduct of the study compliance with the study protocol and follow-up schedule.

Patient deprived of their liberty or under guardianship, curatorship or safeguard of justice.

Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution. Presence or suspicion of active bacterial, fungal or viral infections, or uncontrolled fever.

Major surgery within 2 weeks prior to randomization or have an unhealed operation wounds.

What this study is about