A first in human modular, open-label, phase I/IIa study to evaluate the safety, tolerability, pharmacokinetics and anti-tumour activity of the specific dUTPase inhibitor CV6-168 in combination with anticancer treatments in patients with advanced malignancies.
Advanced malignancies
o This is a non-randomised study o IMPs (Part A) = CV6-168, Folinic Acid, 5-FU CV6-168: p.o.(dose range 50-900 mg) • Cycle 1 on Days 8-10, 15-17 three times daily • All other cycles on Days 1-3, three times daily 5-FU, i.v. bolus 400mg/m2 and i.v. infusion 2400mg/m2 • Cycle 1 o i.v. bolus Day 1, Day 15 o i.v. infusion Day 1-3, 15-17 • All other cycles o i.v. bolus Day 1 o i.v. infusion Day 1-3 Folinic acid, i.v. infusion 350mg (d, l-folinic acid) or 175mg (l-folinic acid) • Cycle 1 o Day 1, Day 15 • All other cycles o Day 1 o Cycle duration is 4 weeks for Cycle 1 and 2 weeks for all other cycles. Each cycle starts the day after the previous cycle ends. o Patients are followed for safety, tolerability, PK, efficacy and PD assessments as detailed in the Outcomes
Module 1 Inclusion Criteria: Inclusion Criteria for Part A (Dose Escalation) & Part B (Dose Expansion) To be eligible for inclusion into this study, each patient must fulfil the following inclusion criteria within 28 days before C1D1: 1. Patients must be aged at least 18 years. 2. An ECOG Performance Score of 0-1. 3. A life expectancy of at least 12 weeks. 4. Patients must be able to swallow oral medications. 5. Women of childbearing potential (WOCBP) must have a negative serum test (minimum sensitivity 25 IU/L or equivalent units of HCG) during screening and within 48 hours prior to the start of investigational product and agree to have regular urine pregnancy testing throughout the trial. WOCBP must agree to use two effective forms of contraception (one highly effective form plus a barrier method) throughout the study and until 6 months after the last study medication administration. A woman is considered as WOCBP, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Post-menopause is defined as: 5.1. Amenorrhea ≥ 12 consecutive months without another cause, or 5.2. For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >35 mIU/mL; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 5.3. For women who have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks before screening. In the case of bilateral oophorectomy alone, the female patient is considered of non-childbearing potential only when the reproductive status of the patient has been confirmed by FSH hormone level assessment. 6. Male patients must agree to use a barrier method of contraception [condom plus spermicide] and refrain from donating sperm from the first administration of IMP, throughout the s
Current key exclusion criteria as of 02/07/2026: Module 1 Exclusion Criteria: Exclusion Criteria for Part A (Dose Escalation) & Part B (Dose Expansion) To be eligible for inclusion into this study, each patient must violate none of the following exclusion criteria within 28 days before C1D1: 1. Patients who received treatment for the malignancy within 28 days before the first dose of IMP. 2. Patients with an active bacterial or viral infection within 7 days before the first dose of IMP. This includes Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2], Herpes Zoster, Varicella Zoster or chickenpox, and any major systemic infection requiring antibiotics or antivirals. 3. Patients with known active hepatitis B or C (mandatory testing not required). 4. Patients with known Human Immunodeficiency Virus (HIV) infection (mandatory testing not required). 5. Patients with any other condition, including mental illness or substance abuse or abnormal laboratory results, deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results. This includes (but is not limited to) the following: 5.1. Congestive heart failure (New York Heart Association Class III or Class IV). 5.2. Clinically significant coronary heart disease or myocardial infarction within 6 months of the first dose of study medication or high risk of uncontrolled arrhythmia. 5.3. Unstable or poorly controlled angina pectoris. 5.4. Complete left bundle branch, fascicular block or other clinically significant abnormal ECG finding. 5.5. QTc interval >470 milliseconds using the Fridericia formula. 5.6. History of or current risk factor for torsade de pointes (e.g., heart failure, hypokalaemia, or a family history of long QT syndrome). 5.7. History of severe skin reactions. 5.8. History of severe ocular disorders. 5.9. Interstitial pneumonitis or pulmonary fibrosis. 5.10. Diabetes mel