e16197 Background: Donafenib (Dona), a multikinase inhibitor recently marketed in China for advanced HCC with its superiority in overall survival (OS) over Sorafenib from a large head-to-head Phase 3 study. The clinical experience of triple therapy (TKIs + ICIs + TACE) in the treatment of patients (pts) with uHCC is limited. We assessed the safety and efficacy of triple therapy [Dona +anti-PD-1+ TACE] in uHCC in this Phase 1 study. Methods: The objective of this Phase 1, open-label, multicenter, dose-escalation and expansion study was to assess the MTD/recommended dose for Dona in combination of a fixed-dose anti-PD-1 plus TACE in uHCC. The primary endpoint was DLT occurring in the first treatment cycle. Secondary endpoints included the overall safety and tolerability, ORR and PFS by mRECIST. Qualified pts (age 18-75) were enrolled if uHCC without macrovascular invasion (VP3/4) or extrahepatic spread; measurable disease by mRECIST; ECOG 0 to 1; Child-Pugh A; systemic therapy naive. Results: At the cut-off date (Dec 31 2021), data of 25 pts who underwent triple therapy from 6 cancer centers in China were analyzed (Table). The median duration of follow-up was 105 days (1-358 days). No DLTs were observed [Dona 50 mg Bid (n=3); 150 mg Qd (n=3); 100 mg Bid (n=6)]. Additional 13 pts were treated with the recommended dose of Dona 100 mg Bid. Treatment-related adverse events (TRAE) occurred in 24 pts (Grade 3, 36%; no Grade 4). 16 pts had at least one response assessment, the ORR was 62.5%; in 12 pts with BLCL B, the ORR was 83.3%. mPFS was not reached. Conclusions: Combination of Dona, anti-PD-1 and TACE showed a high rate of tumor response and good safety profile in uHCC. Clinical trial information: NCT04605185. [Table: see text]
Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage strategy that may increase hepatic tumour resectability and reduce postoperative liver failure rate by inducing rapid hypertrophy of the future liver remnant (FLR). Pathophysiological mechanisms after the first stage of ALPPS are poorly understood. Methods An ALPPS model was established in rabbits with liver VX2 tumour. The pathophysiological mechanisms after the first stage of ALPPS in the FLR and tumour were assessed by multiplexed positron emission tomography (PET) tracers, dynamic contrast-enhanced MRI (DCE-MRI) and histopathology. Results Tumour volume in the ALPPS model differed from post-stage 1 ALPPS at day 14 compared to control animals. 18F-FDG uptake of tumour increased from day 7 onwards in the ALPPS model. Valid volumetric function measured by 18F-methylcholine PET showed good values in accurately monitoring dynamics and time window for functional liver regeneration (days 3 to 7). DCE-MRI revealed changes in the vascular hyperpermeability function, with a peak on day 7 for tumour and FLR. Conclusion Molecular and functional imaging are promising non-invasive methods to investigate the pathophysiological mechanisms of ALPPS with potential for clinical application.
TPS619 Background: 1. Biliary tract cancer (BTC) accounts for 4% of all digestive tract cancers. In 2016-2020, the incidence of BTC has gradually increased worldwide. In China, gallbladder carcinoma accounted for 1.7% of all tumors and 1.9% of deaths in some regions. 2. The standard second-line treatment regimen is mFOLFOX, with an ORR of 5%, PFS of 2 months and OS of 6.2 months. Methods: This is a single-arm, open-label, phase II study, approximately 31 patients of unresectable locally advanced or metastatic BTC with HER2 overexpression will be enrolled. Each treatment cycle is 14 days. Therapeutic regimen: Disitamab Vedotin 2.5mg/kg IV, D1, Q2W + Zimberelimab 240mg IV, D1, Q2W All patients treated until a loss of clinical benefit or unacceptable toxicity is observed by the investigator. Objective: to evaluate the efficacy and safety of Disitamab Vedotin + Zimberelima in patients with unresectable locally advanced or metastatic BTC with HER2 overexpression Disitamab Vedotin: Vedecitumab is an antibody-drug conjugate (ADC), with a humanized antibody conjugated to four tubulin inhibitor molecules (DAR=4) Zimberelimab: Zimberelimab is a fully human IgG4 monoclonal antibody that specifically binds to PD-1 molecules on the surface of lymphocytes. This drug is approved for r/r cHL and is also effective in the cervical cancer. Clinical trial information: NCT05540483 .
Cuprotosis was discovered as a previously unidentified mode of cell death in March 2022. However, the relationship between this novel copper-mediated cell death and non-coding RNA has not been explored in Hepatocellular carcinoma (HCC). We developed a useful predictive model based on the TCGA-LIHC using four cuprotosis-related lncRNAs (AC026401.3, NRAV, CAPN10-DT, and SNHG4). As determined by the Kaplan-Meier survival analysis, the median survival time of those in the high-risk group was significantly lower than that of those in the low-risk group (P<0.001). The risk score (0.772) has a much greater area under the curve (AUC) than the stage (0.671), age (0.531), gender (0.509), or grade (0.499). We used CIBERSORT, QUNANTISEQ, XCELL, CIBERSORT-ABS, EPIC, TIMER, and single-sample gene set enrichment analysis (ssGSEA) to compare immune cell infiltration, immunological function, and immune checkpoint related gene expression. And ssGSEA analysis revealed that the expression of 12 types of immune function genes differed between high- and low-risk groups. In the high-risk group, the expression of genes involved in APC-co-stimulation, checkpoint, human leukocyte antigen (HLA), MHC class I, T cell-co-stimulation, and so on were significantly up-regulated, whereas type I IFN response and type II IFN response were markedly down-regulated. CD274, HAVCR2, CTLA4, VTCN1, CD27, and CD200RL expression levels were all greater in the high-risk group than in the low-risk group, with the exception of ADORA2A. To sum up, the model based on the signature of 4 kinds of cuprotosis-related lncRNAs can effectively assess the prognosis and survival of HCC patients.
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