Targeting glypican-3 as a new frontier in liver cancer therapy

Table 1 Current clinical trials targeting glypican-3

No.	NCT number	Study title	Study status	Stage	Enrollment (estimated)	Primary endpoint
1	NCT05352542	GPC3-targeting CART Cell in Treatment of Advanced Hepatocellular Carcinoma	Terminated	Phase 1	10	Incidence, severity, and type of TEAEs; DLT rate; RP2D finding; CAR positive T cells; CAR transgene levels in peripheral blood
2	NCT02395250	Anti-GPC3 CAR T for Treating Patients with Advanced HCC	Completed	Phase 1	13	AEs attributed to the administration of the anti-GPC3 CAR T cells
3	NCT03146234	CAR-GPC3 T Cells in Patients with Refractory Hepatocellular Carcinoma	Completed	NA	7	Safety and tolerance
4	NCT03980288	4th Generation Chimeric Antigen Receptor T Cells Targeting Glypican-3	Completed	Phase 1	6	DLT and MTD
5	NCT02905188	Glypican 3-specific Chimeric Antigen Receptor Expressing T Cells for Hepatocellular Carcinoma (GLYCAR)	Completed	Phase 1	9	Number of patients with DLT; RP2D
6	NCT03884751	Chimeric Antigen Receptor T Cells Targeting Glypican-3	Completed	Phase 1	9	DLT, MTD
7	NCT02748837	A Study of ERY974 in Patient with Advanced Solid Tumors	Completed	Phase 1	29	Dose escalation: MTD determination; cohort expansion: Preliminary assessment of change in tumor size
8	NCT05070156	B010-A Injection for Treating Patients with GPC3 Positive Advanced Hepatocellular Carcinoma	Active not recruiting	Phase 1	3	Evaluate incidence of TEAEs [safety and tolerability] after B010-A injection
9	NCT02932956	Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Patients with Pediatric Solid Tumors (GAP)	Active not recruiting	Phase 1	10	Number of patients with DLT
10	NCT04405778	A Study of TAK-102 in Adult with Previously-Treated Solid Tumors	Active not recruiting	Phase 1	11	Number of participants with first cycle DLTs; number of participants with one or more TEAE; number of participants with AEs of clinical interest
11	NCT03198546	GPC3-CAR-T Cells for Immunotherapy of Cancer with GPC3 Expression	Recruiting	Phase 1	30	Number of patients with DLT
12	NCT05003895	GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Hepatocellular Carcinoma (HCC)	Recruiting	Phase 1	38	To determine the safety and feasibility of T-cells, expressing a novel humanized anti-GPC3 chimeric antigen receptor, in patients with advanced HCC, expressing GPC3
13	NCT04928677	A Study of Codrituzumab in Children and Young Adults with Solid Tumors and Have Not Responded to Treatment or Have Come Back After Treatment	Recruiting	Phase 1	50	Estimate the MTD
14	NCT06196294	GPC3/Mesothelin-CAR-γδT Cells Against Cancers	Recruiting	Phase 1	30	Number of patients with DLT
15	NCT06461624	Clinical Trial of Autologous GPC3 CAR-T Cells (CBG166) Therapy for Advanced Hepatocellular Carcinoma	Recruiting	Phase 1	15	DLT; AEs; MTD
16	NCT05620706	Study of GPC-3 CAR-T Cells in Treating with Hepatocellular Carcinoma	Recruiting	NA	20	AE/SAE
17	NCT05410717	CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors	Recruiting	Phase 1	200	Safety by CTCAE V5.0
18	NCT05047510	GPC3 Targeted Fluorescence Image Guided Surgery of Hepatocellular Carcinoma	Recruiting	NA	60	HCC lesions (numbers of intraoperatively detected hepatocellular carcinoma lesions)
19	NCT05779917	Mesothelin/GPC3/GUCY2C-CAR-T Cells Against Cancers	Recruiting	Phase 1	30	Number of patients with DLT
20	NCT06383520	Study on the Clinical Application Value of PET Imaging Targeting GPC3 in Hepatocellular Carcinoma	Recruiting	Early Phase 1	100	Visual and standardized uptake values assessment of lesions and biodistribution
21	NCT05926726	GPC3-directed CAR-T in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma	Recruiting	NA	12	TRAEs; DLT; RP2D of JWATM214 in HCC patients
22	NCT06687941	A Study to Evaluate the Tolerability, Safety, and PK of AST-201 in Patients With GPC3-positive Advanced Solid Tumors	Recruiting	Phase 1	70	DLT
23	NCT06726161	Study of the Theranostic Pair RYZ811 (diagnostic) and RYZ801 (therapeutic) to Identify and Treat Subjects with GPC3+ Unresectable HCC	Recruiting	Phase 1	70	Evaluate RYZ801 dose and safety; Evaluate RYZ811 safety and distribution
24	NCT03198052	GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR-T Cells Against Cancers	Recruiting	Phase 1	30	Number of patients with DLT
25	NCT06652243	Clinical Study of SN301A Injection in the Treatment of Hepatocellular Carcinoma	Recruiting	Phase 1	12	DLT; Incidence and severity of AEs and SAEs (safety and tolerability)
26	NCT06478693	A Study of MT-303 in Adults With Advanced or Metastatic GPC3-Expressing Cancers, Including HCC	Recruiting	Phase 1	48	Type, incidence and severity of AEs; RP2D; change from baseline in vital signs; change in laboratory parameters; change from baseline in ECG parameters
27	NCT06084884	A Phase I/II Study to Evaluate AZD5851 in GPC3+ Advanced/Recurrent Hepatocellular Carcinoma	Recruiting	Phase 1 Phase 2	94	Incidence of participants with DLTs, AEs, including AESIs and SAEs; determination of the recommended dose of AZD5851 for expansion phase
28	NCT05120271	BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors	Recruiting	Phase 1; Phase 2	110	Dose limiting toxicity; MTD; RP2D; TEAEs
29	NCT05783570	To Evaluate the Safety, Tolerability and Preliminary Efficacy of EU307	Recruiting	Phase 1	12	AEs (including DLT); production of replication competent lentiviruses; development of anti-drug antibodies
30	NCT04377932	Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors	Recruiting	Phase 1	24	Number of patients with DLT
31	NCT04715191	Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors	Recruiting	Phase 1	24	Number of patients with DLT
32	NCT06427941	A Phase 1 Study of BGB-B2033, Alone or in Combination With Tislelizumab, in Participants With Advanced or Metastatic Solid Tumors	Recruiting	Phase 1	70	DLT
33	NCT05103631	Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for Solid Tumors	Recruiting	Phase 1	27	Number of patients with DLT
34	NCT06088459	NWRD06 DNA Plasmid for HCC After Radical Resection	Recruiting	Phase 1	9	DLT; all AEs
35	NCT04756648	Phase I Clinical Trial of CT0180 Cells in the Treatment of Hepatocellular Carcinoma	Recruiting	Phase 1	21	DLT; MTD; AE; AESI
36	NCT06560827	CT011 Autologous CAR-T Cells in Patients With Hepatocellular Carcinoma at Risk of Recurrence After Surgical Resection	Recruiting	Phase 1	30	Incidence and severity of TEAE; incidence and severity of TRAE; incidence and severity of AESI
37	NCT04842812	Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors	Recruiting	Phase 1	40	Safety of TILs/CAR-TILs treatment in advanced solid cancers
38	NCT06715839	Target-specific immunoPET Imaging of Digestive System Carcinoma	Recruiting	NA	400	Biodistribution; standardized uptake value; radiation dosimetry; diagnostic value in patients with digestive system malignancy; the correlation between the expression of specific target and tracer uptake value
39	NCT05263830	Glypican-3 as a Prognostic Factor in Patients With Hepatocellular Carcinoma Treated by Immunotherapy	Recruiting	NA	120	Evaluate concentration of circulating GPC-3
40	NCT04506983	GPC3-CAR-T Cells for the Hepatocellular Carcinoma	Suspended	Phase 1	12	Percentage of AEs
41	NCT06815432	GPC-3 CAR T CELLS for Recurrent GPC-3 Positive Glioblastoma	Not yet recruiting	Phase 1	27	Number of patients with DLT
42	NCT06641453	CAR-T Cell Therapy Targeting GPC3 in Patients with Advanced GPC3-Positive Hepatocellular Carcinoma	Not yet recruiting	Phase 1; Phase 2	30	Incidence of TRAEs; incidence of DLTs
43	NCT06198296	Immunotherapy for Adults with GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells	Not yet recruiting	Phase 1	21	Number of patients with DLT
44	NCT06590246	A Study to Evaluate C-CAR031 in Glypican-3 (GPC3)+ Advanced/recurrent Hepatocellular Carcinoma (HCC)	Not yet recruiting	Phase 1; Phase 2	121	Safety and tolerability; anti-tumor activity
45	NCT06795022	First in Human Study to Evaluate AZD9793 in Participants With Advanced or Metastatic Solid Tumours	Not yet recruiting	Phase 1; Phase 2	304	Number of patients with AEs; number of patients with SAEs; number of patients with AESIs; number of patients with DLT; objective response rate
46	NCT02723942	CAR-T Cell Immunotherapy for HCC Targeting GPC3	Withdrawn	Phase 1; Phase 2	0	Radiological assessment
47	NCT04093648	T Cells co- Expressing a Second Generation Glypican 3-specific Chimeric Antigen Receptor With Cytokines Interleukin-21 and 15 as Immunotherapy for Patients With Liver Cancer (TEGAR)	Withdrawn	Phase 1	0	DLT rate
48	NCT04121273	GPC3-targeted CAR-T Cell for Treating GPC3 Positive Advanced HCC	Unknown	Phase 1	20	Number of patient with dose limiting toxicity
49	NCT03084380	Anti-GPC3 CAR-T for Treating GPC3-positive Advanced Hepatocellular Carcinoma (HCC)	Unknown	Phase 1; Phase 2	20	Safety: Measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
50	NCT03130712	A Study of GPC3-targeted T Cells by Intratumor Injection for Advanced HCC (GPC3-CART)	Unknown	Phase 1; Phase 2	10	Safety of CAR-T cell infusion mediated by intratumoral injection as measured by number of participants with AEs
51	NCT02715362	A Study of GPC3 Redirected Autologous T Cells for Advanced HCC	Unknown	Phase 1; Phase 2	30	Safety of CAR-T cell infusion mediated by TAI as measured by number of participants with AEs
52	NCT05344664	Novel GPC3 CAR-T Cell Therapy for Hepatocellular Carcinoma	Unknown	Phase 1	12	Percentage of AEs
53	NCT02876978	Anti-GPC3 CAR T for Recurrent or Refractory Lung Squamous Cell Carcinoma	Unknown	Phase 1	20	Safety and tolerance: Occurrence of study related AEs
54	NCT04076137	Targeted T-cell Therapy in Solid Tumors	Unknown	Early Phase 1	10	Overrall survival
55	NCT03146637	Study of Activated CIK Armed With Bispecific Antibody for Advanced Liver Cancer	Unknown	Phase 2	80	Overrall survival
56	NCT04728139	Assessment of Glypican 3 as Apredictive Marker in Colorectal Cancer Patients	Unknown	NA	90	Evaluation of Glypican 3 role as a predictive and diagnostic marker of colorectal marker
57	NCT05059821	Personalized Cancer Vaccine in Egyptian Cancer Patients	Unknown	Phase 1	10	Assessment of the safety of the personalized cancer vaccine; assessment of immunological response

DLT: Dose limiting toxicity; RP2D: Recommended Phase 2 dose; MTD: Maximum tolerated dose; AE: Adverse event; SAE: Serious adverse event; AESI: Adverse event of special interest; TEAE: Treatment-emergent adverse event; TRAE: Treatment-related adverse event; GPC3: Glypican-3