Zepsun (donafenib) / Suzhou Zelgen - LARVOL DELTA

Hepatic Arterial Infusion Chemotherapy Combined with Donafenib and PD-1 Inhibitor for Advanced Hepatocellular Carcinoma with Lung Metastases: A Multicenter Retrospective Study (APASL 2026) - No abstract available

Metastases • Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor

Combinatorial treatment with donafenib and quercetin suppresses lipid metabolism in HepG2 cells by targeting the CREB1/DRP1/SREBP1 axis. (PubMed, Transl Cancer Res) - "These findings indicate that the combination of QUE and DON exerts its antitumor effects by inhibiting the CREB1/DRP1/SREBP1 axis mediated lipid metabolism pathway in HepG2 cells. This offers a novel potential approach for enhancing the therapeutic efficacy of DON in the treatment of HCC."

Journal • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • CREB1

PULSAR Combined With Fecal Microbiota Transplantation for Advanced Hepatocellular Carcinoma Progressing After First-Line Targeted-Immunotherapy (clinicaltrials.gov) - P2 | N=64 | Not yet recruiting | Sponsor: Wang Xin

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor • Transplantation

PATH: Study on the Safety and Efficacy of Donafinib Combined With Anti-PD-1 Antibody as Adjuvant Therapy for HCC Patients (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Zhejiang University | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Nov 2025 | Trial primary completion date: Dec 2023 ➔ Nov 2025

Trial completion • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor

Drug Sensitivity Testing-Based Tumor Organoids to Guide Adjuvant Therapy After Hepatectomy for Primary Liver Cancer (clinicaltrials.gov) - P2 | N=56 | Not yet recruiting | Sponsor: Eastern Hepatobiliary Surgery Hospital

New P2 trial • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

A Phase II Trial of Organoid Drug Sensitivity Testing to Guide Therapy in Unresectable Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=94 | Not yet recruiting | Sponsor: Eastern Hepatobiliary Surgery Hospital

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Synergistic antitumor effect of oroxylin A and donafenib in hepatocellular carcinoma through tumor protein p53 signaling pathway activation. (PubMed, World J Gastroenterol) - "Oroxylin A and donafenib exert a synergistic anti-tumor effect in HCC by co-activating the TP53 signaling pathway through distinct but complementary molecular axes. This combination strategy presents a promising and viable therapeutic approach to overcome the limitations of donafenib monotherapy in the treatment of HCC."

Journal • Fibrosarcoma • Hepatocellular Cancer • Oncology • Sarcoma • Solid Tumor • CDK9 • MDM4

Effect of Huaier Granule on Nephrotoxicity Associated With Targeted Therapy for Advanced Hepatobiliary Malignancies. (clinicaltrials.gov) - P2 | N=76 | Completed | Sponsor: Fudan University | Recruiting ➔ Completed | Phase classification: P4 ➔ P2 | N=53 ➔ 76 | Trial completion date: Apr 2025 ➔ Dec 2025 | Trial primary completion date: Feb 2025 ➔ Sep 2025

Adverse events • Enrollment change • Phase classification • Trial completion • Trial completion date • Trial primary completion date • Biliary Cancer • Oncology

Effects of Cytochrome P450 enzymes and drug-drug interaction on donafenib metabolism: in vivo, in vitro and in silico. (PubMed, Bioorg Chem) - "This study systematically elucidated the metabolic characteristics of the hepatocellular carcinoma (HCC) therapeutic drug donafenib and its drug-drug interaction (DDI) with the antiviral agent arbidol. Moreover, Tmax was prolonged by 68.42%, while CLz/F was decreased by 53.85%. These results provided critical references for clinical dosage adjustment, facilitating personalized treatment and reducing the risk of adverse reactions."

Journal • Preclinical • Hepatocellular Cancer • Oncology • Solid Tumor • CYP3A4

A phase Ⅱ, single-arm, exploratory study of GEMOX regimen combined with tislelizumab and donafenib in the perioperative treatment of potentially resectable intrahepatic cholangiocarcinoma with high risk of recurrence (ChiCTR) - P2 | N=20 | Not yet recruiting | Sponsor: Hunan Provincial People's Hospital; Hunan Provincial People's Hospital

New P2 trial • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

Prospective Cohort Study on the Efficacy and Safety of Sequential TIPS-TACE/HAIC Combined or Not Combined with Donafenib and Tislelizumab in the Treatment of BCLC Stage C Hepatocellular Carcinoma Patients with Concomitant Portal Hypertension (ChiCTR) - P=N/A | N=96 | Not yet recruiting | Sponsor: Beijing Youan Hospital, Capital Medical University; Beijing Youan Hospital, Capital Medical University

New trial • Cardiovascular • Hepatocellular Cancer • Hypertension • Oncology • Portal Hypertension • Solid Tumor • Thrombosis

Donafenib monotherapy or combined with PD-1/L1 inhibitors or transcatheter arterial chemoembolization as adjuvant therapy in hepatocellular carcinoma patients with high-risk recurrence after radical resection, a multi-cohort clinical study. (ChiCTR) - P=N/A | N=90 | Recruiting | Sponsor: The First Affiliated Hospital of Harbin Medical University; The First Affiliated Hospital of Harbin Medical University

New trial • Hepatocellular Cancer • Oncology • Solid Tumor • AFP

Exploratory Clinical Study of TACE Combined with Iparomlimab and Tuvonralimab and Donafenib in Conversion Therapy for Unresectable Locally Advanced and Advanced Hepatocellular Carcinoma (ChiCTR) - P=N/A | N=42 | Not yet recruiting | Sponsor: The First Affiliated Hospital of University of science and technology of China; The First Affiliated Hospital of University of science and technology

New trial • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Pharmacokinetics and Individualized Dose Optimization of Donafenib in Hepatocellular Carcinoma Patients after Transjugular Intrahepatic Portosystemic Shunt (TIPS) (ChiCTR) - P=N/A | N=20 | Not yet recruiting | Sponsor: Beijing Youan Hospital, Capital Medical University; Beijing Youan Hospital, Capital Medical University

New trial • Hepatocellular Cancer • Oncology • Solid Tumor

GEMOX Combined With Donafenib and Tislelizumab in Advanced Biliary Tract Carcinoma (clinicaltrials.gov) - P2 | N=93 | Recruiting | Sponsor: Fudan University | Trial primary completion date: Sep 2026 ➔ Dec 2026

Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor

FOLFOX-HAIC Combined With Donafenib and Pucotenlimab as First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Sun Yat-sen University

New P2 trial • Biliary Cancer • Cholangiocarcinoma • Hepatocellular Cancer • Oncology • Solid Tumor

Donafenib in locally advanced/metastatic, radioactive iodine-refractory, differentiated thyroid cancer: A randomized, double-blind, placebo-controlled, multi-center phase III clinical trial (DIRECTION) (ESMO 2022) - P3 | "No treatment-related death was observed. Conclusions Donafenib well balanced the efficacy and safety, suggesting its potential to be an alternative for patients with progressive RAIR-DTC."

Clinical • P3 data • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Stereotactic body radiotherapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) versus TACE and TKIs alone for unresectable hepatocellular carcinoma (uHCC) with portal vein tumor thrombus (PVTT): A randomized controlled trial. (ASCO 2024) - "TKIs (sorafenib 0.4g bid; donafenib 0.2g bid; or lenvatinib 8mg/12mg qd, depending on body weight) were paused during the perioperative period of TACE (up to 4 times). In uHCC patients with PVTT, the combination of SBRT and TACE-TKIs showed significant survival benefit without the identification of any severe safety concerns."

Clinical • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Hypertension • Liver Failure • Oncology • Solid Tumor • Thrombosis

Donafenib and sintilimab plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A phase II, biomarker exploratory study (DosinTACE). (ASCO-GI 2026) - P2 | "DosinTACE study demonstrates that the combination of TACE, donafenib, and sintilimab shows promising efficacy and a manageable safety profile in patients with uHCC. Moreover, tumor-intrinsic metabolic and immune disparities drive treatment response variability."

Biomarker • IO biomarker • P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Donafenib intolerance in hepatocellular carcinoma: severe hand-foot skin reaction and successful switch to lenvatinib - a case report and literature review. (PubMed, Front Oncol) - "This case highlights the importance of early detection and accurate grading of HFSR, timely treatment interruption, and mechanism-informed switching to an alternative tyrosine kinase inhibitor such as lenvatinib. It also underscores key differences in toxicity profiles between donafenib-associated with VEGFR/RAF-related cutaneous injury-and lenvatinib, which is more commonly linked to hypertension, diarrhea, and appetite or weight changes."

Journal • Cardiovascular • Dermatology • Hepatocellular Cancer • Hypertension • Oncology • Pain • Solid Tumor

CHANCE 2203: HAIC Combined With Donafenib and Sintilimab for Unresectable ICC (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: Zhongda Hospital | Recruiting ➔ Completed | Trial completion date: Jul 2023 ➔ Oct 2025 | Trial primary completion date: Jun 2023 ➔ Oct 2025

Trial completion • Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

LncRNA ZFAS1 in hepatocellular carcinoma: A systematic review of molecular mechanisms and clinical translation. (PubMed, Noncoding RNA Res) - "Clinically, plasma ZFAS1 demonstrates enhanced diagnostic utility when combined with alpha-fetoprotein (AUC = 0.891), while therapeutic targeting of ZFAS1-mediated PI3K-AKT and PERK/ATF4 pathways shows promise in overcoming sorafenib/donafenib resistance. Current translational challenges include ZFAS1 isoform heterogeneity, suboptimal liquid biopsy sensitivity, and dynamic TME interactions. Future directions should employ multi-omics integration (spatial transcriptomics/single-cell sequencing) coupled with AI-driven network modeling to systematically decode ZFAS1's regulatory architecture, ultimately enabling precision theranostic strategies for HCC management."

Journal • Review • Hepatocellular Cancer • Oncology • Solid Tumor • AFP • AIFM2 • ATF4 • MET • MIR150 • MIR193A • MMP14 • ZEB1 • ZFAS1

Neo-TACE: Neoadjuvant HAIC of TACE Plus Donafenib in BCLC B Stage HCC: a Multi-center Randomized Controlled Trial. (clinicaltrials.gov) - P2/3 | N=18 | Terminated | Sponsor: Peking University | N=156 ➔ 18 | Trial completion date: Dec 2027 ➔ Oct 2025 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2026 ➔ Oct 2025; Difficult to enroll participants

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hepatocellular Cancer • Oncology • Solid Tumor

Case Report: Successful Surgical Resection of PVTT Vp4 Hepatocellular Carcinoma Following Hepatic Arterial Infusion Chemotherapy Combined with Cadonilimab Plus Donafenib. (PubMed, Pharmgenomics Pers Med) - "Following multidisciplinary team evaluation, the patient received conversion therapy consisting of hepatic artery infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin, in combination with cadonilimab and donafenib...This regimen may substantially improve oncological outcomes and enable curative resection. This case provides compelling evidence to support further clinical investigation of this multimodal therapeutic combination."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • Thrombosis • AFP

Efficacy and safety analysis of donafenib combined with PD-1 inhibitors with or without chemotherapy in patients with advanced BTC: A retrospective study (ESMO Asia 2025) - "Donafenib and anti-PD-1 antibodies with or without Chemotherapy as a 1L treatment option for advanced BTC patients shows favorable efficacy and tolerability."

Metastases • Retrospective data • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology