Zepsun (donafenib) / Suzhou Zelgen - LARVOL DELTA

Comparison of the efficacy of transarterial chemoembolization combined with different molecular targeted agents and/or immune checkpoint inhibitors for unresectable hepatocellular carcinoma: a systematic review and network meta-analysis. (PubMed, J Gastrointest Oncol) - "For OS, TACE + anlotinib + sintilimab (TACE + Anl + Sin), TACE + donafenib + toripalimab (TACE + Don + Tor), TACE + lenvatinib + tislelizumab (TACE + Len + Tis), TACE + sorafenib + camrelizumab (TACE + Sor + Cam), and TACE + apatinib + camrelizumab (TACE + Apa + Cam) were all significantly superior to TACE alone...For PFS, compared with TACE alone, TACE + Anl + Sin, TACE + Don + Tor, TACE + lenvatinib + pembrolizumab (TACE + Len + Pem), TACE + Len + Tis, and TACE + Apa + Cam significantly prolonged PFS...For DCR, TACE + Len + Tis showed the best performance, while TACE + atezolizumab + bevacizumab (TACE + Ate + Bev), TACE + Anl + Sin, and TACE + Apa + Cam also demonstrated relatively high DCR. Compared with TACE alone, TACE combined with MTAs and ICIs can significantly improve outcomes in patients with uHCC. TACE + Anl + Sin, TACE + Len + Tis, and TACE + Apa + Cam may be promising treatment options, although more prospective studies are needed for further validation."

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

Hepatic arterial infusion chemotherapy combined with donafenib and camrelizumab in the treatment of unresectable hepatocellular carcinoma with portal vein tumor thrombus: A prospective single-arm study (ESMO 2026) - No abstract available

Clinical • Hepatocellular Cancer • Oncology • Solid Tumor

A Clinical Study of Gecacitinib Combined with Donafenib and Tislelizumab for Patients with Unresectable Hepatocellular Carcinoma (ChiCTR) - P4 | N=39 | Not yet recruiting | Sponsor: Chongqing University Cancer Hospital; Chongqing University Cancer Hospital

New P4 trial • Hepatocellular Cancer • Oncology • Solid Tumor

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

Magnitude of Survival Benefit Associated With Tyrosine Kinase Inhibitors in Advanced Thyroid Carcinoma: A Systematic Review and Meta-Analysis Incorporating Updated Long-Term Evidence From SELECT (Lenvatinib) and COSMIC-311 (Cabozantinib) Trials. (PubMed, World J Oncol) - "This systematic review and meta-analysis integrates recent randomized evidence, including donafenib and nintedanib, with qualitative synthesis of updated SELECT (lenvatinib) and COSMIC-311 (cabozantinib) analyses, alongside separate quantitative evaluations of placebo-controlled and dose-comparison trials...Although placebo-controlled trials consistently favored TKIs, dose-comparison trials did not demonstrate superiority of higher-dose regimens. Further randomized studies with longer follow-up and biomarker-guided treatment strategies are warranted."

Journal • Retrospective data • Review • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Tislelizumab combined with donafenib and GEMOX as first-line treatment for advanced biliary tract cancer: A single-arm, phase II study. (ASCO 2026) - P1/2, P2 | "Gemcitabine and oxaliplatin (GEMOX) plus tislelizumab and donafenib as the first-line treatment for advanced BTC has confirmed good safety and preliminary efficacy in our phase I study (NCT04979663). GEMOX plus tislelizumab and donafenib as a first line treatment option for advanced BTC patients shows favorable efficacy and tolerability."

Clinical • Metastases • P2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor • Thrombocytopenia

Epalrestat Combined With HAIC, Donafenib and Tislelizumab as First-line Treatment for Patients With Unresectable HCC and Diabetes (clinicaltrials.gov) - P2 | N=32 | Not yet recruiting | Sponsor: Haibo Shao | Initiation date: Jun 2026 ➔ Oct 2026

Trial initiation date • Diabetes • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor

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

Enrollment open • Hepatocellular Cancer • Oncology • Solid Tumor • Transplantation

Donafenib in Locally Advanced or Metastatic Thyroid Cancer: A Retrospective Real-World Study (ETA 2026) - "Donafenib exhibits favorable anti-tumor efficacy and manageable safety in real-world advanced thyroid cancer. ECOG performance status and pathological subtype are reliable prognostic biomarkers, providing robust real-world evidence for individualized donafenib-based precision therapy."

Metastases • Real-world • Real-world evidence • Retrospective data • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

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

A Prospective, Single-Arm, Open-Label Clinical Study of the Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy Combined With Targeted Therapy and a PD-1 Inhibitor in Patients With Postoperative Hepatocellular Carcinoma and Microvascular Invasion (clinicaltrials.gov) - P4 | N=40 | Not yet recruiting | Sponsor: Zhai Wenlong

New P4 trial • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Efficacy and safety of transarterial chemoembolization combined with donafenib and camrelizumab for hepatocellular carcinoma with portal vein tumor thrombus: a dual-center, retrospective propensity score-matched analysis. (PubMed, Front Immunol) - "This retrospective PSM analysis observed a correlation between TACE+D+C triple therapy and longer survival and higher tumor response among PVTT-positive HCC patients. Given the inherent limitations of a retrospective observational design, these results cannot establish therapeutic superiority, and prospective randomized controlled trials are warranted to validate causal clinical benefits."

Journal • Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor • Thrombosis

The Efficacy and Safety of Donafenib Plus PD-1/L1 Monoclonal Antibodies Plus TACE or HAIC as First-line Treatment for Unresectable Hepatocellular Carcinoma A Multi-center, Retrospective Clinical Study (clinicaltrials.gov) - P=N/A | N=400 | Not yet recruiting | Sponsor: Shanghai Zhongshan Hospital

New trial • Hepatocellular Cancer • Oncology • Solid Tumor

Dapagliflozin Add-on in Unresectable HCC With Metabolic Syndrome (clinicaltrials.gov) - P2 | N=44 | Not yet recruiting | Sponsor: Sun Yat-sen University

New P2 trial • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor

Comparative efficacy and prognostic analysis of different targeted-immunotherapy regimens in advanced hepatocellular carcinoma (EASL 2026) - "Patients were categorized into four groups: lenvatinib plus a PD-1 inhibitor (n=226), bevacizumab plus a PD-1 inhibitor (n=73), donafenib plus a PD-1 inhibitor (n=37), and apatinib plus camrelizumab (n=24)...Subgroup analyses revealed comparable OS between bevacizumab plus atezolizumab and bevacizumab plus sintilimab (28 months, 95% CI: 20-38 vs. 42 months, 95% CI: 30-47, P=0.116), as well as between lenvatinib plus pembrolizumab and lenvatinib plus tislelizumab (27 months, 95% CI: 24-38 vs. 28 months, 95% CI: 22-37, P=0.693)... In this real-world cohort, first-line lenvatinib-, bevacizumab-, and donafenib-based PD-1 inhibitor combinations demonstrated comparable survival outcomes in advanced HCC. Achieving an objective response and successful conversion to curative surgery were independent favorable prognostic factors, highlighting the critical importance of tumor downstaging and surgical eligibility in optimizing long-term survival."

Clinical • Metastases • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

The Application of Locoregional Therapy Combined With Systemic Therapy in the Perioperative Period of Huge Hepatocellular Carcinoma: A Retrospective Cohort Study (clinicaltrials.gov) - P=N/A | N=715 | Completed | Sponsor: Tongji Hospital

New trial • Hepatocellular Cancer • Oncology • Solid Tumor

A Real-world Study of Immunotherapy Combination Regimens for Treating Liver Cancer in Cold Regions (clinicaltrials.gov) - P=N/A | N=1000 | Active, not recruiting | Sponsor: Harbin Medical University

New trial • Real-world evidence • Cholangiocarcinoma • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Donafenib suppresses glioblastoma progression: potential enhancement of therapeutic response in TMZ-resistant models. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Glioblastoma (GBM) is the most aggressive primary brain tumor of the central nervous system and remains largely incurable due to the development of resistance to temozolomide (TMZ). While PAMPA analysis indicated that DNF exhibits lower blood-brain barrier (BBB) permeability than TMZ, in silico modeling revealed that a substantial proportion of its metabolites may possess BBB-penetrating potential. Collectively, these findings suggest that DNF exerts antitumor effects in both TMZ-sensitive and TMZ-resistant GBM models and highlight its potential as a promising therapeutic candidate for further investigation."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • STAT3

Hepatic Artery Infusion Chemotherapy Plus Donafenib in Patients With Hepatocellular Carcinoma After Surgery (clinicaltrials.gov) - P2 | N=30 | Completed | Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Not yet recruiting ➔ Completed | Trial completion date: Aug 2024 ➔ Sep 2025 | Trial primary completion date: Mar 2024 ➔ Sep 2025

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

In vitro Evaluation of the Effects of Donafenib on TMZ-Resistant Glioblastoma and Microglia Polarization (EACR 2026) - "Standard treatment includes surgical resection followed by radiotherapy and temozolomide (TMZ). DNF exerts strong antitumor effects in GL261 cells by inhibiting key oncogenic signaling pathways. Although synergy analysis indicated mostly antagonistic interactions, functional assays demonstrated that selected combinations, particularly the half-dose combination, enhanced antitumor activity. These findings suggest that DNF may represent a promising therapeutic strategy in GBM by targeting tumor cells and the tumor microenvironment."

Preclinical • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • KDR

TACE plus donafenib and immune checkpoint inhibitors for intermediate HCC (CHANCE2410 study): a propensity score matching analysis. (PubMed, Eur Radiol Exp) - "Large real-world studies evaluating the combination therapy of TACE plus donafenib and ICIs for intermediate HCC patients are scarce. The combination therapy significantly improved PFS, OS, and ORR compared to TACE monotherapy, with a manageable safety profile. TACE plus donafenib and ICIs could serve as an alternative option for intermediate HCC."

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

DEB-TACE-HAIC combined with donafenib and camrelizumab in the treatment of unresectable hepatocellular carcinoma: a multicenter retrospective study. (PubMed, Front Immunol) - "Among patients with uHCC, the DHDC quadruple regimen was associated with improved survival outcomes while maintaining an acceptable safety profile. These findings suggest that a treatment strategy incorporating DEB-TACE-HAIC in combination with targeted therapy and immunotherapy may represent a more effective therapeutic option for selected patients with uHCC, warranting further prospective investigation."

Journal • Retrospective data • Cardiovascular • Fibrosis • Hematological Disorders • Hepatitis B • Hepatocellular Cancer • Immunology • Infectious Disease • Liver Cancer • Oncology • Solid Tumor • Thrombosis

Locally advanced or metastatic thyroid cancer treated with donafenib with or without chemotherapy: A real-world study. (ASCO 2026) - "Our prior research demonstrated that anlotinib combined with chemotherapy exhibited favorable efficacy and safety as a first-line treatment for anaplastic thyroid carcinoma (ATC) and primary squamous cell carcinoma of the thyroid. This real-world study suggests that donafenib either as monotherapy or in combination with chemotherapy is both effective and well-tolerated in patients with locally advanced or metastatic thyroid cancer."

Clinical • Metastases • Real-world • Real-world evidence • Oncology • Pulmonary Disease • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

Unveiling the Power of Deuterium in Drug Discovery: A Comprehensive Overview. (PubMed, MedComm (2020)) - "Although some deuterated drugs, notably donafenib and deutetrabenazine, have demonstrated clinically significant efficacy, their limited use is an effect of ongoing challenges with metabolic switching and species-specific variation, as well as inadequate mechanistic understanding...Furthermore, the review's discussion includes the current challenges, synthesis, analytical limits, and regulatory considerations that influence further development. Overall, the review offers a strategic roadmap for utilizing deuterium-enabled molecular engineering to accelerate the development of next-generation precision medicine, guiding rational design, innovation toward safer, longer-lasting, and more effective treatments."

Journal • Review • CNS Disorders • Oncology • Rare Diseases • Targeted Protein Degradation

Efficacy and safety of transarterial therapy combined with donafenib plus PD-1 inhibitors for unresectable hepatocellular carcinoma: A multicenter retrospective study. (ASCO 2026) - P4 | "The PD-1 inhibitors administered included tislelizumab (41.4%), camrelizumab (37.1%), sintilimab (18.6%), toripalimab (2.9%). This real-world study demonstrates that transarterial therapy combined with donafenib and PD-1 inhibitors provides encouraging survival outcomes and a manageable safety profile for uHCC patients."

Retrospective data • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Liver Failure • Oncology • Solid Tumor