tremelimumab联合durvalumab（MEDI4736）（T300+D）治疗合并Child-Pugh-B肝硬化的晚期肝细胞癌的II期单臂研究（STRIDE in CP-B）

Background: In registration phase 3 studies, most patients enrolled had Child-Pugh (CP)-A cirrhosis, with CP-B cirrhosis are often excluded from clinical trials, yet in clinical practices, patients are often treated with new agents without efficacy or safety data. Therefore, there is an unmet need to evaluate the efficacy and safety of therapeutics in patients with HCC and CP-B cirrhosis. Based on results from the HIMALAYA trial, tremelimumab and durvalumab (T300+D) is FDA-approved for HCC. In this trial, grade 3/4 treatment-related adverse events (TRAEs) occurred in 25.8% (T300+D), 12.9% (durvalumab), and 36.9% (sorafenib) of patients. Therefore, we hypothesize that T300+D will be safe and tolerated in CP-B patients with HCC, and the safety of efficacy of T300+D in patients with CP-B cirrhosis should be investigated. Purpose: Results from this study may establish T300+D as a first-line therapy for CP-B patients with HCC, and therefore, could be practice-changing and set precedence for future studies dedicated to investigating newer agents for CP-B with HCC. Methods: Single-arm, phase II study of patients with advanced HCC who are eligible for first-line treatment with T300+D [NCT06526104]. Priming dose of tremelimumab 300 mg intravenously (IV) once (Cycle 1, Day 1 only) with durvalumab 1500 mg IV on Day 1 of each 4-week cycle. Primary Objective: compare the percentage of grade 3 or higher TRTE-AEs with T300+D in patients with CP-B cirrhosis with historical controls of VEGF-targeting therapies. Secondary Objective(s): objective response rate (ORR), overall survival (OS), progression-free survival (PFS), associations of baseline albumin-bilirubin (ALBI) grade with PFS/OS and grade 3/4 AEs with T300+D. Exploratory endpoint: evaluate QOL at baseline and during treatment with T300+D, EORTC-QLQ-C30 and QLQ-HCC18 questionnaires. Inclusion criteria: Patients diagnosed with HCC based on pathologic diagnosis from biopsy or radiographic diagnosis on CT liver or MRI liver (i.e., Barcelona Clinic Liver Cancer (BCLC) stage B and not candidate for locoregional therapies or BCLC stage C), no prior systemic therapies, Child-Pugh-B7 or -B8 liver cirrhosis, and ECOG 0-1. . This study will achieve 80% power for testing H­ o : p D300+T =p Historical versus H 1 ­: p D300+T ≠ p Historical at alpha=0.05 with n=30 subjects. Progress: The study began enrollment in 12/2024, with 13 patients enrolled to the date of abstract submission. Three sites are opening soon with planned completion of enrollment at the end of 2026. Conclusion: After 15 patients are enrolled, enrollment will be held pending further review if there is sufficient evidence to suggest that the true probability of (possibly, probably, or definitely) treatment-related, grade 3-5 adverse events exceeds 60%. Results will be presented soon after.