Alimentary pharmacology & therapeutics · 2026
Clinical Trial: Early Nivolumab Addition to Regorafenib in Patients With Hepatocellular Carcinoma in Second-Line (The GOING Trial).
СтатьяКлиническое исследование II фазыКлиническое исследование I фазыНазвание и аннотация: Перевод пока не подготовлен
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Sanduzzi-Zamparelli Marco, Matilla Ana, Lledo José Luis, Muñoz-Martínez Sergio, Varela María, Iñarrairaegui Mercedes, Perelló Christie, Mínguez Beatriz, Llarch Neus, Márquez Laura, Guerrero Antonio, Iserte Gemma, Castaño-García Andrés, Carrión Laura, Fortuny Marta, Rimola Jordi, García-Criado Ángeles, Domenech Gema, Torres Ferran, Rios-Guillermo José, Boix Loreto, Samper Esther, Kateb Àngels, Bruix Jordi, Reig Maria
Аннотация
BACKGROUND & AIMS: Highly effective second-line treatments for hepatocellular carcinoma remain an unmet need. The GOING investigator-initiated Phase I/IIa trial evaluated regorafenib plus nivolumab (add-on) in patients who progressed on sorafenib (Cohort-A) or discontinued atezolizumab-bevacizumab (Cohort-B).
METHODS: Patients received regorafenib for two 28-day cycles, adding nivolumab in cycle 3, until unacceptable adverse events, symptomatic progression, withdrawal or death. Primary endpoint was safety. Secondary endpoints included overall survival, time to progression, post-progression survival, objective response rate and incidence of new-extrahepatic-spread.
RESULTS: Of 85 patients screened, 67 were enrolled (75.5% BCLC-C). All experienced adverse events and 9% led to discontinuation. Severe treatment-related adverse events occurred in 28.4% overall, 32.1% in Cohort-A, and 14.3% in Cohort-B. Median overall survival was 20.0 (95% CI 11-37) months, with 40.6% survival at 36 months. In Cohort-A, median overall survival was 25 (95% CI 14-39) months with 45% survival at 36 months, while Cohort-B median overall survival was 8 (95% CI 4-NE) months with 28.6% survival at 24 months. Objective response rate was 16.4%; median time to progression and post-progression survival were 5 (95% CI 4-9) months and 14 (95% CI 8-33) months. Intrahepatic growth was the most common progression pattern, followed by new-extrahepatic-spread.
CONCLUSIONS: The add-on strategy of regorafenib plus nivolumab in second-line had manageable safety and significant clinical activity with a noteworthy median overall survival of 20 months. Among those progressing on sorafenib, 45% were alive at 3 years. These findings support further evaluation with mechanism-guided trials after progression on immunotherapy.
TRIAL REGISTRATION: EudraCT number: 2019-003108-10; https://www.clinicaltrialsregister.eu.
METHODS: Patients received regorafenib for two 28-day cycles, adding nivolumab in cycle 3, until unacceptable adverse events, symptomatic progression, withdrawal or death. Primary endpoint was safety. Secondary endpoints included overall survival, time to progression, post-progression survival, objective response rate and incidence of new-extrahepatic-spread.
RESULTS: Of 85 patients screened, 67 were enrolled (75.5% BCLC-C). All experienced adverse events and 9% led to discontinuation. Severe treatment-related adverse events occurred in 28.4% overall, 32.1% in Cohort-A, and 14.3% in Cohort-B. Median overall survival was 20.0 (95% CI 11-37) months, with 40.6% survival at 36 months. In Cohort-A, median overall survival was 25 (95% CI 14-39) months with 45% survival at 36 months, while Cohort-B median overall survival was 8 (95% CI 4-NE) months with 28.6% survival at 24 months. Objective response rate was 16.4%; median time to progression and post-progression survival were 5 (95% CI 4-9) months and 14 (95% CI 8-33) months. Intrahepatic growth was the most common progression pattern, followed by new-extrahepatic-spread.
CONCLUSIONS: The add-on strategy of regorafenib plus nivolumab in second-line had manageable safety and significant clinical activity with a noteworthy median overall survival of 20 months. Among those progressing on sorafenib, 45% were alive at 3 years. These findings support further evaluation with mechanism-guided trials after progression on immunotherapy.
TRIAL REGISTRATION: EudraCT number: 2019-003108-10; https://www.clinicaltrialsregister.eu.