Zepsun (donafenib) / Suzhou Zelgen - LARVOL DELTA

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

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, 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

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

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

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

Donafenib, anti-PD-1 antibodies, plus HAIC as conversion therapy in patients with initially unresectable HCC:A prospective, single-arm, phase II study (ESMO Asia 2025) - P4 | "The triple combination of donafenib, anti-PD-1 antibodies, and HAIC exhibits favorable efficacy and tolerability, positioning it as a clinically feasible conversion strategy for initially unresectable HCC."

Clinical • P2 data • Hepatocellular Cancer • Oncology

FOLFOX-HAIC combined with sintilimab and donafenib for advanced hepatocellular carcinoma: A single-arm, phase II study (ESMO Asia 2025) - "The combination of mFOLFOX6-HAIC with sintilimab and donafenib exhibited an encouraging short-term efficacy for advanced HCC by improving the ORR and DCR, with acceptable toxicity. We will report more data in the future."

Metastases • P2 data • Hepatocellular Cancer • Oncology • Solid Tumor

Adjuvant donafenib combined with PD-1 for hepatocellular carcinoma with high-risk recurrence factors after radical resection: A sIPTW adjusted retrospective cohort study (Adhere study) (ESMO Asia 2025) - "Adjuvant donafenib combined with PD-1 could improve RFS compared to active surveillance in Chinese HCC patients with high-risk recurrence factors after radical resection."

Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor • PD-1

TACE-HAlC combined with Donafenib and immune checkpoint inhibitors for BCLC stage C HCC patients (THEME study): a retrospective IPTW-adjusted cohort study. (PubMed, Front Immunol) - "Among these the incidence of grade ≥3 AE was 40.8% in the quadruple therapy group and 38.6% in the targeted-immunotherapy group. Compared with targeted-immunotherapy group, patients with BCLC stage C HCC treated with TACE-HAIC combined with donafenib and ICIs demonstrated superior efficacy and acceptable safety."

Checkpoint inhibition • Journal • Retrospective data • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Correction: TACE-HAlC combined with Donafenib and immune checkpoint inhibitors for BCLC stage C HCC patients (THEME study): a retrospective IPTW-adjusted cohort study. (PubMed, Front Immunol) - "[This corrects the article DOI: 10.3389/fimmu.2025.1669856.]."

Checkpoint inhibition • Journal • Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor

AZ-628 sensitizes donafenib in hepatocellular carcinoma by targeting tyrosine kinase pathway and ferroptosis. (PubMed, Cytojournal) - "The HCC cells HepG2 and SNU449 were treated with five drugs, namely, dimethyl sulfoxide, AZ-628, SU-5402, TG-101209, and SPP-86, combined with donafenib to determine half-maximal inhibitory concentration values...Ferrous ion (Fe2+) and reactive oxygen species levels were measured after Erastin/RSL3 induction...In vivo experiments demonstrated a combined anti-tumor efficacy of AZ-628 and donafenib in HCC models (P < 0.0001). The findings of this study reveal a new combination therapy targeting the TK pathway for the treatment of HCC and provide a theoretical foundation for addressing donafenib resistance."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • EGR1

Development of an UPLC-MS/MS method for quantification of donafenib and its metabolite in rat plasma: application to drug-drug interaction. (PubMed, Biochem Pharmacol) - "In vivo, the AUC(0-t), AUC(0-∞) and Cmax of donafenib and donafenib N-oxide were significantly increased in the presence of efavirenz, which indicated that efavirenz increased the exposure of donafenib in rats. In short, this UPLC-MS/MS method was reliable for quantifying donafenib and its metabolite, and the findings suggested that efavirenz had an inhibitory effect on the metabolism of donafenib in vitro and in vivo."

Journal • Preclinical • Hepatocellular Cancer • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor