Study of CT-01 as Monotherapy and Combination Therapy in Subjects With Intermediate or Advanced Hepatocellular Carcinoma
brief summary
This is a Phase 1, open-label, multicenter, dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CT-01, administered either as monotherapy or in combination with everolimus. The study population includes subjects with intermediate or advanced hepatocellular carcinoma (HCC) who have progressed on, or are intolerant to, at least one prior line of systemic treatment. All available standard-of-care therapies should have been received, if deemed appropriate by the investigator (unless contraindicated or considered inappropriate by the treating physician). Eligible subjects are classified as Barcelona Clinic Liver Cancer (BCLC) stage B or C and must not be amenable to curative treatment approaches. Only subjects with preserved liver function (Child-Pugh Class A, score 5-6) at screening are eligible. Approximately 141 participants will be enrolled across 20 sites in Europe (France, Spain, and Germany).
detailed description
This is an open-label, multicenter study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of CT-01 in subjects with advanced hepatocellular carcinoma (HCC). The study consists of two sequential parts.
Part 1 investigates CT-01 as monotherapy and includes a dose-escalation phase (Part 1A) followed by a dose-expansion phase (Part 1B). A Bayesian Optimal Interval (BOIN) design will be used, with up to seven predefined dose levels. Additional subjects may be enrolled to backfill dose levels of interest. Treatment will be administered in 28-day cycles, with dose-limiting toxicities (DLTs) assessed during Cycle 1. Dose decisions will be made by an Independent Data Monitoring Committee (IDMC), with input from a Safety Monitoring Committee (SMC).
Part 2 evaluates CT-01 in combination with everolimus and includes a dose-escalation phase (Part 2A) and a dose-expansion phase (Part 2B). Up to four dose levels are planned in Part 2A, with starting doses informed by Part 1 results. As in Part 1, DLTs will be assessed during Cycle 1 and reviewed by the IDMC and SMC.
official title
A Phase 1, Open-Label, Dose Escalation, and Dose Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CT-01 as Monotherapy and Combination Therapy With Everolimus in Subjects With Intermediate or Advanced Hepatocellular Carcinoma (BCLC Stage B or C) With Preserved Liver Function (Child-Pugh Class A)