Zepsun (donafenib)

The multi-kinase inhibitor donafenib offers superior survival benefits over sorafenib. These findings highlight the potential of FADS2 as a biomarker for HCC and show a promising combinatorial therapy for its treatment. Thus, we provide a theoretical basis for translating laboratory research into clinical applications.

P4, N=70, Not yet recruiting, The First Affiliated Hospital with Nanjing Medical University

P=N/A, N=25, Not yet recruiting, Zhongshan Hospital; Zhongshan Hospital

P=N/A, N=40, Recruiting, HenanCancerHospital; HenanCancerHospital

P2, N=13, Recruiting, The First Affiliated Hospital with Nanjing Medical University; The First Affiliated Hospital with Nanjing Medical University

P2/3, N=52, Not yet recruiting, Nanjing Drum Tower Hospital; Nanjing Drum Tower Hospital

P=N/A, N=97, Active, not recruiting, First Hospital of China Medical University

P=N/A, N=108, Recruiting, Sun Yat-sen University

P=N/A, N=204, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Donafenib combined with HAIC in the treatment of unresectable HCC patients can notably reduce serum AFP levels, improve hepatic fibrosis, enhance short-term efficacy, prolong PFS, and have a favorable safety profile.

P2, N=93, Recruiting, Fudan University | N=35 --> 93 | Trial completion date: Mar 2025 --> Mar 2027 | Trial primary completion date: Sep 2024 --> Sep 2026

P2, N=30, Completed, Shanghai Zhongshan Hospital | Recruiting --> Completed

TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.

P2, N=30, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=45, Recruiting, Anhui Provincial Hospital

P4, N=32, Not yet recruiting, Tongji Hospital

Currently, a total of six small molecule tyrosine kinase inhibitors (TKIs) have been approved for aHCC, including first-line sorafenib, lenvatinib, and donafenib, and second-line regorafenib, cabozantinib, and apatinib. These TKIs improved patients survival, which are associated with disease stage, etiology, liver function, tumor burden, baseline levels of alpha-fetoprotein, and treatment history. This review focuses on the clinical outcomes of these TKIs in key clinical trials, retrospective and real-world studies and discusses the future perspectives of TKIs for aHCC, with an aim to provide up-to-date evidence for decision-making in the treatment of aHCC.

P2, N=75, Recruiting, West China Hospital

These data suggest that the combination of donafenib and a PARP1 inhibitor results in more significant DNA damage in cells and promotes cell apoptosis. Thus, the combination of donafenib and PARP1 inhibitors has the potential to be a treatment option for liver cancer.

P1/2, N=130, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Recruiting

P4, N=53, Recruiting, Fudan University | Trial completion date: Jun 2024 --> Apr 2025 | Trial primary completion date: May 2024 --> Feb 2025

Median progression-free survival and overall survival were 9 and 14 months, respectively. TACE, camrelizumab, and donafenib combination therapy in Chinese advanced HCC patients show effectiveness in extending survival with low severe AEs incidence.

CREB3 overexpression contributed to Donafenib resistance in HCC cells by activating the ZFAS1/p65 axis.

P1, N=40, Recruiting, Peking Union Medical College Hospital

P1, N=18, Active, not recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P=N/A, N=279, Completed, Zhejiang University

P2, N=38, Recruiting, Wuhan Union Hospital, China

P2, N=56, Completed, Guangxi Medical University

P1/2, N=130, Not yet recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd

P2/3, N=156, Recruiting, Peking University | Trial primary completion date: Dec 2023 --> Jun 2024

No significant differences were found in the incidence or severity of adverse events between the TACE+DP and TACE+D groups (any grade: 92.9% vs. 94.6%, P=0.270; grade 3 or 4: 33.8% vs. 37.3%, P=0.253). With favorable safety and tolerability, TACE combined with donafenib and PD-1 inhibitors significantly improved PFS, OS, and ORR compared to TACE combined with donafenib.

Clinical Trial Registration Number NCT05253053 Sponsored by No funding sources reported Background: Programmed Cell Death Ligand 1 (PD-L1) inhibitor durvalumab in combination with gemcitabine and cisplatin has been approved as first-line therapy for BTC...Another pt with prior immunotherapy (sintilimab), target therapy (donafenib) and chemotherapy had a tumor reduction of 39.1% (tinengotinib 10 mg QD plus atezo)... Tinengotinib in combination with atezo was well-tolerated for the treatment of Chinese BTC pts. Preliminary encouraging efficacy of tinengotinib in combination with atezo was observed in pts with heavily pre-treated BTC. The ongoing study is to further evaluate the safety and efficacy of tinengotinib in combination with atezo in pts with BTC who had prior immunotherapy and/or chemotherapy.

P1/2, N=35, Not yet recruiting, Sichuan Cancer Hospital ; Sichuan Cancer Hospital | Phase classification: P=N/A --> P1/2

The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.

Systemic treatment with molecularly targeted drugs and immune checkpoint inhibitors, such as sorafenib, lenflutinib, donafenib, atezolizumab plus bevacizumab, sintilimab plus IBI305, regorafenib, pembrolizumab and anti-Cytotoxic T Lymphocyte antigen 4 (CTLA-4) was recommended by guidelines, but with limited effectiveness for HCC patients with PVTT. In recent years, the comprehensive treatment of HCC has advanced greatly. This review aims to provide an insight into the treatment modalities available for HCC patients with PVTT.

A chromosome conformation capture assay confirmed that the increased expression of HMOX1 is caused by the significantly enhanced interaction between the promoter and upstream enhancer under dual-drug combination. Taken together, this study elucidates a new synergistic lethal interaction in liver cancer.

Donafenib was well-tolerated, and demonstrated clinical benefit in terms of improved PFS, ORR and DCRin patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for RAIR-DTC patients.

P2, N=20, Recruiting, Beijing Tsinghua Chang Gung Hospital | Not yet recruiting --> Recruiting | Initiation date: Oct 2022 --> Mar 2023

GEMOX combined with donafenib plus tislelizumab as the first-line therapy for unresectable BTC showed manageable toxicity and encouraging efficacy especially in terms of promising conversion rate in Stage III patients.

Lenvatinib was generally cost-effective in most studies, but not compared to donafenib or sorafenib (if the price sorafenib was significantly discounted).

In hepatocellular carcinoma treatment, sorafenib, oxaliplatin, 5-fluorouracil, capecitabine, lenvatinib, and donafenib are first-line drugs; regorafenib, apatinib, and cabozantinib are second-line drugs; and oxycodone, morphine, and fentanyl are commonly used analgesics...The precision and accuracy of all analytes were < 7.21% and 5.62%, respectively. Our study provides empirical support for a simple, reliable, specific, and suitable technique for clinical TDM and pharmacokinetics.

P1b, N=19, Terminated, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Terminated; Corporate policy adjustments