PreprintCommunicationVersion 1Preserved in Portico This version is not peer-reviewed
Sequential Therapy with Ropeginterferon Alfa-2b and Anti-PD1 for Inhibiting Recurrence of Hepatitis B-related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results
Version 1
: Received: 6 December 2023 / Approved: 6 December 2023 / Online: 7 December 2023 (03:04:15 CET)
Version 2
: Received: 7 December 2023 / Approved: 7 December 2023 / Online: 8 December 2023 (02:53:09 CET)
Version 3
: Received: 8 December 2023 / Approved: 8 December 2023 / Online: 8 December 2023 (12:37:22 CET)
Qin, A.; Wu, C.-R.; Ho, M.-C.; Tsai, C.-Y.; Chen, P.-J. Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results. Int. J. Mol. Sci.2024, 25, 433.
Qin, A.; Wu, C.-R.; Ho, M.-C.; Tsai, C.-Y.; Chen, P.-J. Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results. Int. J. Mol. Sci. 2024, 25, 433.
Qin, A.; Wu, C.-R.; Ho, M.-C.; Tsai, C.-Y.; Chen, P.-J. Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results. Int. J. Mol. Sci.2024, 25, 433.
Qin, A.; Wu, C.-R.; Ho, M.-C.; Tsai, C.-Y.; Chen, P.-J. Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results. Int. J. Mol. Sci. 2024, 25, 433.
Abstract
In hepatocellular carcinoma (HCC), recurrence usually occurs after curative surgical resection. Currently, no adjuvant therapy has shown to reduce recurrence rates. In our study, the effect of sequential treatment with recombinant mouse-IFN-α (rmIFN-α) and anti-mouse-PD1 in hepatitis B virus (HBV) clearance was evaluated in mouse model. A phase I trial was conducted to assess the safety, tolerability, and inhibitory effect of sequential therapy with ropeginterferon alfa-2b and nivolumab in HCC recurrence in patients undergone curative surgery for HBV-related HCC. HBV suppression was significantly greater with rmIFN-α and anti-PD1 sequential treatment than with mono-administration in a mouse model. In the Phase I trial, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks at 450 µg for six doses, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease or clearance of HBV surface antigen was observed in two patients. Dose-limiting toxicity of grade 3 aspartate aminotransferase and alanine transaminase increases was observed in one patient. The maximum tolerated dose was determined. No HCC recurrence was observed. The treatment modality was well tolerated by the patients. These data support further clinical development of sequential therapy as a post-surgery prophylactic measure against HCC recurrence.
Medicine and Pharmacology, Medicine and Pharmacology
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