GPC3 positive

Metastatic HCC is a rare encounter for dermatopathologists. We aim to increase awareness of its occurrence in patients with advanced HCC and highlight the importance of clinical correlation when faced with poorly differentiated or unusual-looking basaloid neoplasms.

P=N/A, N=12, Not yet recruiting, The First People's Hospital of Lianyungang; The First People's Hospital of Lianyungang | Initiation date: May 2024 --> Sep 2024

Thereby, [68Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.

Finally, we revealed that GLUT1 or AGK maintained anti-apoptosis ability in CD8+ T cells via activation of the PI3K/Akt pathway. This finding might identify a therapeutic strategy for advanced HCC.

This chip was further employed in clinical plasma samples and showed that the number of GPC3-positive EVs isolated from hepatocellular carcinoma patients was significantly higher than that of healthy individuals. This ExoCPR chip may provide a promising tool for EV-based liquid biopsy and other fundamental research.

Furthermore, the tumor-to-organ ratios of [18F]AlF-NOTA-IPB-GPC3P surpassed those of [18F]AlF-GP2633. Our results support the utilization of [18F]AlF-NOTA-IPB-GPC3P as a PET imaging agent targeting the GPC3 receptor for tumor detection.

P2, N=30, Recruiting, Eureka Therapeutics Inc. | Trial completion date: Dec 2027 --> Dec 2026

P2, N=24, Recruiting, Eureka Therapeutics Inc. | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

P2, N=24, Recruiting, Eureka Therapeutics Inc. | Phase classification: P1/2 --> P2

A combined model including AP Rad-score and serum AFP levels based on contrast-enhanced CT could preoperatively predict GPC3-positive expression in HCC.

Therapeutically, significant and durable tumor regression and survival benefit were achieved with 177Lu- and 225Ac-labeled RAYZ-8009, as single agents and in combination with lenvatinib, in GPC3-positive HCC xenografts. Preclinical in vitro and in vivo data demonstrate the potential of RAYZ-8009 as a theranostic agent for the treatment of patients with GPC3-positive HCC.

P1/2, N=24, Recruiting, Eureka Therapeutics Inc. | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024 | N=12 --> 24

P1, N=3, Active, not recruiting, Tongji University | Recruiting --> Active, not recruiting | Trial completion date: Sep 2022 --> Sep 2024 | Trial primary completion date: Aug 2022 --> Aug 2024

P1/2, N=106, Recruiting, Sanofi | Trial completion date: May 2030 --> Dec 2030 | Trial primary completion date: May 2030 --> Dec 2030

P1/2, N=84, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P=N/A, N=8, Not yet recruiting, the Affiliated Drum Tower Hospital, Medical School of Nanjing University; Nanjing Zilong Biotechnology Co., LTD | .

The nomogram combining multiparametric MRI and clinical indicators is found to have satisfactory predictive efficacy for preoperative prediction of GPC3-positive HCC. Accordingly, the proposed method can promote individualized risk stratification and further treatment decisions of HCC patients.

The MRI-confirmed patient cohort indicated that there was a positive correlation between total tumor size and GPC3-positive exosome concentration (r:0.78 and p<0.001). We developed an immunocapture assay that can be used for simultaneous isolation and quantification of HCC-derived exosomes from a small serum volume with high accuracy.

P1, N=9, Recruiting, Newish Technology (Beijing) Co., Ltd.

DCA also showed that the nomogram had the highest net clinical benefit for predicting GPC3 expression.In the validation cohort, the ROC curve results showed predicted GPC3-positive expression nomogram model AUC, sensitivity, and specificity of 0.800, 58.5%, and 100.0%, respectively. HBP radiomics features are closely associated with GPC3-positive expression, and combined clinicoradiologic factors and radiomics features nomogram may provide an effective way to non-invasively and individually screen patients with GPC3-positive HCC.

P1/2, N=84, Not yet recruiting, AstraZeneca

GPC3 protein is expressed in a large percentage of HB and FLC tumors, but with variable intensity and distribution. Characterization of GPC3 tumor protein H-score and pattern of immunoreactivity are two independent parameters that may be helpful to quantitate GPC3 immunostaining of tumor and correlate with treatment response to a variety of GPC3 targeted therapeutics.

The present work revealed that FXR could be combined with GPC3 in distinguishing between HCC and non-neoplastic hepatic lesions with improved specificity rather than using an individual marker.

P1/2, N=81, Not yet recruiting, Boston Pharmaceuticals, Inc.

CT017 CAR T cells were engineered to co-express CAR-GPC3 and runt-related transcription factor 3 (RUNX3), which triggers CD8 T-cell infiltration into the cancer microenvironment...These results need to be confirmed in a robust clinical trial. This study was funded by CARsgen Therapeutics Co., Ltd.

The tumour-to-liver SI ratio on the HBP combined with serum AFP >20 ng/ml and non-smooth tumour margin are potential predictive factors for GPC3 expression of small HCC ≤3cm. GPC3 expression is correlated with a poor prognosis in HCC patients.

Specific immunohistochemical stains and clinical and laboratory data are critical for an accurate diagnosis. An immunohistochemical panel including markers for yolk sac tumor (such as glypican3 and SALL4) can usually help establish the diagnosis.

Preoperative integration of CEUS features and clinical factors can non-invasively and effectively identify GPC3-positive HCC patients, providing valuable assistance in making personalized treatment decisions.

Decision curve analysis further demonstrates the clinical practicality of the nomogram. Multi-phase CE-MRI based on the delta-radiomics model can non-invasively predict GPC3-positive HCC and can be a useful method for individualized diagnosis and treatment.

Figure: Figure 1. Histopathology of hepatoid adenocarcinoma of the esophagus in H&E stain (1A), with positive IHC findings in pancytokeratin stain (1B), CDX-2 (1C), and glypican-3 (1D), at magnification x40.

Autoimmune hepatitis, PBC and the overlap syndrome are less associated with the development of liver cirrhosis and HCC than other chronic liver diseases, especially if other risk factors are not associated. This case highlights the importance of a proper surveillance of cirrhotic patients every 6 months including abdominal ultrasound and AFP levels is crucial for an early diagnosis of a HCC.

Conclusions These preliminary results from the first two DLs suggest that SAR444200 is tolerable at the tested DLs in patients with advanced solid tumors. Dose escalation continues at this time.

Lymphodepletion regimen comprised fludarabine 25 mg/m2 and cyclophosphamide 300 mg/m2 daily for 3 days...Grade 1 cytokine release syndrome was observed in 6 patients; tocilizumab was given in one patient and no glucocorticoids were used... CT0180 demonstrated manageable safety profile and promising antitumor potential. Further exploration of CT0180 in HCC is needed. Clinical trial information: NCT04756648.

P1/2, N=106, Recruiting, Sanofi | Trial completion date: May 2029 --> May 2030 | Trial primary completion date: May 2029 --> May 2030

Improving NK cell culture protocol is crucial for NK-based therapies. This study shows that IL-21 plays key roles into NK cell biology, enhancing memory-like properties of cytokine-activated NK cells. Cytotoxicity is further augmented by addition of GPC3-specific CAR, offering a promising venue for HCC therapy.

Bifunctional deferoxamine (DFO) isothiocyanate was used to synthesize native HN3 (nHN3)-DFO... Zr-ssHN3 showed clear advantages in tumor uptake and tumor-to-liver signal ratio over the conventionally modified Zr-nHN3 in xenograft models. Our results establish the potential of HN3-based single-domain antibody probes for GPC3- directed PET imaging of liver cancers.

P1, N=30, Recruiting, Second Affiliated Hospital of Guangzhou Medical University | Trial completion date: Aug 2024 --> Aug 2029 | Trial primary completion date: Aug 2022 --> Aug 2025

The superagonistic monoclonal anti-human CD28 antibody (IgG4κ) TGN1412 was used as comparator. Activity is maintained while it allows well tailorable dose response with reduced cytokine release. Compounds are currently in extensive pre-clinical assessment 999