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25d
A Study of Codrituzumab in Children and Young Adults with Solid Tumors and Have Not Responded to Treatment or Have Come Back After Treatment (clinicaltrials.gov)
P1, N=50, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026
Trial completion date • Trial primary completion date
|
GPC3 (Glypican 3)
|
codrituzumab (RG7686)
2ms
Enrollment open
2ms
A First-in-human Study to Learn About the Safety of BAY 3547926 and How Well it Works in Participants With Advanced Liver Cancer (clinicaltrials.gov)
P1, N=148, Not yet recruiting, Bayer | Trial completion date: Feb 2029 --> Dec 2033 | Trial primary completion date: Nov 2027 --> Jul 2030
Trial completion date • Trial primary completion date
3ms
Dose Escalation and Expansion Study of SAR444200-based Regimen in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=33, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting | N=106 --> 33 | Trial completion date: Dec 2030 --> Dec 2025 | Trial primary completion date: Dec 2030 --> Dec 2025
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase) • GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
Tecentriq (atezolizumab) • SAR444200
3ms
Idarubicin-loaded chitosan nanobubbles to improve survival and decrease drug side effects in hepatocellular carcinoma. (PubMed, Nanomedicine (Lond))
To enhance their action, a targeting agent, such as the humanized anti-GPC3 antibody GC33 (condrituzumab), could be attached to their surface. In HUH7 tumor-bearing xenograft mice, CS-NBs loaded with idarubicin and conjugated or not conjugated with 4A1 were both able to slow tumor growth, to increase mouse survival time compared to free idarubicin (p = 0.00044 and 0.0018, respectively) as well as to reduce drug side effects. CS-NBs loaded with idarubicin can be a useful drug delivery strategy for HCC treatment.
Journal • Adverse events
|
GPC3 (Glypican 3)
|
idarubicin hydrochloride • codrituzumab (RG7686)
4ms
Clinical Study of SN301A Injection in the Treatment of Hepatocellular Carcinoma (clinicaltrials.gov)
P1, N=12, Recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Not yet recruiting --> Recruiting
Enrollment open • Metastases
|
cyclophosphamide • fludarabine IV • SENTI-301A
5ms
New P1 trial • Metastases
6ms
Enrollment open
|
Tevimbra (tislelizumab-jsgr)
7ms
A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma (clinicaltrials.gov)
P1, N=179, Active, not recruiting, Chugai Pharmaceutical | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
|
GPC3 (Glypican 3)
|
Avastin (bevacizumab) • Tecentriq (atezolizumab) • Actemra IV (tocilizumab) • ERY974
7ms
Enrollment open
|
GPC3 (Glypican 3)
|
BOS-342
8ms
Glypican-3 deficiency in liver cancer upregulates MAPK/ERK pathway but decreases cell proliferation. (PubMed, Am J Cancer Res)
To confirm the usefulness of the models for GPC3-targeted drug development, we evaluated the target engagement of a GPC3-selective antibody, GC33, conjugated to the positron-emitting zirconium-89 (89Zr) in subcutaneous murine xenografts of wild type (WT) and KO liver cancer cell lines...KO lines demonstrated increased sensitivity to ERK (GDC09994), while AKT (MK2206) inhibition was more effective in WT lines...We show that GPC3-KO liver cancer cell lines exhibit decreased tumorigenicity and altered signaling pathways, including upregulated pMAPK/ERK1/2, compared to parental lines. Furthermore, we successfully distinguished between GPC3+ and GPC3- tumors using the GPC3-targeted immunoPET imaging agent, demonstrating the potential utility of these cell lines in facilitating GPC3-selective drug development.
Journal
|
GPC3 (Glypican 3)
|
MK-2206 • codrituzumab (RG7686)
8ms
Preparation of bacterial outer membrane vesicles with anti-GPC3 single-chain antibody and identification of their targeting effects on hepatocellular carcinoma (PubMed, Sheng Wu Gong Cheng Xue Bao)
The Hbp-hGC 33-OMVs prepared in this study demonstrated stronger ability of binding to Hep G2 cells than the wild-type OMVs (P=0.008). All the data indicated that Hbp-hGC 33-OMVs with anti-GPC3 single-chain antibody were successfully prepared and could be used for research on the targeted therapy of hepatocellular carcinoma.
Journal
|
GPC3 (Glypican 3)
|
codrituzumab (RG7686)
9ms
A Study of MT-303 in Adults With Advanced or Metastatic GPC3-Expressing Cancers, Including HCC (clinicaltrials.gov)
P1, N=48, Recruiting, Myeloid Therapeutics | Not yet recruiting --> Recruiting
Enrollment open • Metastases
9ms
New P1 trial • Metastases
9ms
Development of GPC3-CAR-NK cells and optimization as a therapy for HCC. (PubMed, J Leukoc Biol)
Finally, the combination of microwave ablation with GC33-G2D-NK cell administration showed greater CAR-NK infiltration and tumor regression in ablated tumors than monotherapy alone. These findings indicate that administration of GPC3-CAR-NK cells may be a potential strategy for the treatment of HCC, and regional delivery or their combination with microwave ablation may optimize their efficacy against HCC and may have translational value.
Journal
|
GPC3 (Glypican 3)
|
codrituzumab (RG7686)
9ms
Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors (clinicaltrials.gov)
P1, N=40, Recruiting, Second Affiliated Hospital of Guangzhou Medical University | Trial primary completion date: Dec 2025 --> Dec 2029
Trial primary completion date • Metastases
12ms
ARYA3: T-Cell Therapy (ECT204) in Adults With Advanced HCC (clinicaltrials.gov)
P2, N=30, Recruiting, Eureka Therapeutics Inc. | Trial completion date: Dec 2027 --> Dec 2026
Trial completion date • Metastases
|
GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
cyclophosphamide • Stivarga (regorafenib) • ECT204
1year
ARYA3: T-Cell Therapy (ECT204) in Adults With Advanced HCC (clinicaltrials.gov)
P2, N=24, Recruiting, Eureka Therapeutics Inc. | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026
Trial completion date • Trial primary completion date • Metastases
|
GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
ECT204
1year
ARYA3: T-Cell Therapy (ECT204) in Adults With Advanced HCC (clinicaltrials.gov)
P2, N=24, Recruiting, Eureka Therapeutics Inc. | Phase classification: P1/2 --> P2
Phase classification • Metastases
|
GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
ECT204
1year
Artificial intelligence (AI)-powered quantification of glypican-3 (GPC3) expression facilitates patient selection for GPC3-targeted therapy in solid tumors (AACR 2024)
FFPE slides were stained for GPC3+ (GC33, Ventana), PD-L1+ (22C3, Dako) cells and then scanned at 20x using the Aperio Versa8 scanner... Here we profiled GPC3 expression across tumor types and showed high level of expression in HCC followed by SQ-NSCLC. We have established an AI-powered digital pathology platform that can provide a standardized, scalable, and reproducible method of characterizing GPC3 positivity to support further patient selection in clinical study.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • GPC3 (Glypican 3)
|
PD-L1 expression • GPC3 expression
|
PD-L1 IHC 22C3 pharmDx
|
codrituzumab (RG7686)
1year
A Phase I Study of ERY974 in Patients With Hepatocellular Carcinoma (clinicaltrials.gov)
P1, N=179, Recruiting, Chugai Pharmaceutical | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Dec 2025
Trial completion date • Trial primary completion date • Metastases
|
GPC3 (Glypican 3)
|
Avastin (bevacizumab) • Tecentriq (atezolizumab) • Actemra IV (tocilizumab) • ERY974
over1year
ARYA3: ECT204 T-Cell Therapy in Adults With Advanced HCC (clinicaltrials.gov)
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
Enrollment change • Trial completion date • Trial primary completion date • Metastases
|
GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
ECT204
over1year
Trial completion date • Trial primary completion date • CAR T-Cell Therapy • Metastases
|
cyclophosphamide • ECT204
over1year
Dose Escalation and Expansion Study of SAR444200-based Regimen in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=106, Recruiting, Sanofi | Trial completion date: May 2030 --> Dec 2030 | Trial primary completion date: May 2030 --> Dec 2030
Trial completion date • Trial primary completion date • Metastases
|
ALK (Anaplastic lymphoma kinase) • GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
Tecentriq (atezolizumab) • SAR444200
over1year
Genetically engineered nano-melittin vesicles for multimodal synergetic cancer therapy. (PubMed, Bioeng Transl Med)
VAM generated from the cellular plasma membrane was bio-synthetically fabricated, with the recombinant protein (hGC33 scFv-melittin) being harbored and displayed on the cell membrane...Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co-delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM-based strategies represent a universal, promising approach to multimodal synergetic cancer therapy.
Journal
|
MMP14 (Matrix Metallopeptidase 14)
|
doxorubicin hydrochloride • codrituzumab (RG7686)
over1year
New P1 trial • CAR T-Cell Therapy • Metastases
|
cyclophosphamide • ECT204
over1year
NWRD06 DNA Plasmid for HCC After Radical Resection (clinicaltrials.gov)
P1, N=9, Recruiting, Newish Technology (Beijing) Co., Ltd.
New P1 trial
|
GPC3 (Glypican 3)
|
GPC3 positive
over1year
A novel bispecific antibody as an immunotherapeutic agent in hepatocellular carcinoma. (PubMed, Mol Immunol)
GC33, a humanized mAb directed against GPC3, is a safe and well-tolerated therapy choice for patients with HCC, which tested in a phase I trial in advanced HCC patients...CD16A activation and increased cytokines release were associated with higher anti-tumor activity. In conclusion, this bispecific antibody may possibly help develop new therapeutic strategies for HCC and develop new treatment options in the future.
Journal • IO biomarker
|
GPC3 (Glypican 3) • FCGR3A (Fc Fragment Of IgG Receptor IIIa)
|
GPC3 expression
|
codrituzumab (RG7686)
over1year
New P1/2 trial
|
GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
BOS-342
over1year
Phase I/II open-label study on an anti-GPC3 T cell engager, SAR444200, in patients with advanced solid tumors: Preliminary dose escalation results (ESMO 2023)
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.
Clinical • P1/2 data • Metastases
|
IFNG (Interferon, gamma) • IL6 (Interleukin 6) • GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
SAR444200
almost2years
A Study of Codrituzumab in Children and Young Adults With Solid Tumors and Have Not Responded to Treatment or Have Come Back After Treatment (clinicaltrials.gov)
P1, N=50, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025
Trial completion date • Trial primary completion date
|
GPC3 (Glypican 3)
|
GPC3 expression
|
codrituzumab (RG7686)
almost2years
Dose Escalation and Expansion Study of SAR444200 in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=106, Recruiting, Sanofi | Trial completion date: May 2029 --> May 2030 | Trial primary completion date: May 2029 --> May 2030
Trial completion date • Trial primary completion date • Metastases
|
GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
Libtayo (cemiplimab-rwlc) • SAR444200
almost2years
Derivation and Preclinical Characterization of CYT-303, a Novel NKp46-NK Cell Engager Targeting GPC3. (PubMed, Cells)
In vivo, CYT-303 showed no toxicity or cytokine release in cynomolgus monkeys up to the highest dose (60 mg/kg), administered weekly by intravenous infusion for 28 days. These results demonstrate the potential of CYT-303 to be a safe and effective therapy against HCC.
Preclinical • Journal
|
GPC3 (Glypican 3)
|
GPC3 expression
|
NY-303
2years
CYT-303 FLEX-NKTM engager dose response efficacy mechanisms in HCC tumor model and safety in cynomolgus monkey toxicology studies support clinical evaluation in hepato-cellular carcinoma (AACR 2023)
CYT-303 efficacious doses identified in the HCC model together with safety in cynomolgus monkeys and planned human pharmacokinetic modeling studies support clinical evaluation of CYT-303 in first in human HCC clinical trials.
Preclinical
|
GPC3 (Glypican 3)
|
GPC3 expression
|
NY-303
2years
SENTI-301A, an off-the-shelf multi-armed preclinical CAR-NK cell therapy, for the treatment of GPC3 expressing tumors (AACR 2023)
SENTI-301A is a novel off-the-shelf preclinical CAR-NK cell therapy candidate that targets GPC3-expressing tumors in an antigen-specific manner and exhibits increased persistence via crIL-15. We are exploring the potential synergy between SENTI-301A and CPIs to enhance the existing antitumor functions of SENTI-301A. SENTI-301A is planned for clinical development with an investigational new drug application (IND) expected in 2023.
Preclinical
|
IFNG (Interferon, gamma) • GPC3 (Glypican 3) • GZMB (Granzyme B) • IL15 (Interleukin 15)
|
GPC3 expression
|
SENTI-301A
2years
Improved anti-tumor immune functions of iPSC-derived NK cells with TGFβR2 knock-out and/or IL-15 knock-in by TALEN® editing for use alone or in combination with GPC3 Flex-NKTM bispecific antibody (AACR 2023)
This work demonstrates that KI of IL-15 and KO of TGFβR2 is a promising strategy for TALEN®-engineered iNK cell therapies to overcome the immunosuppressive TME and mount a potent and persistent anti-tumor immune response. The data also provide a solid foundation for combining these edited iNK cells with CYT-303 to address the immunosuppressive TME towards a cure for HCC.
Combination therapy
|
GPC3 (Glypican 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • TGFB1 (Transforming Growth Factor Beta 1) • IL15 (Interleukin 15) • NKG2D (killer cell lectin like receptor K1)
|
GPC3 expression
|
NY-303
2years
Novel GPC3xCD3 (NILK-2501) and GPC3xCD28 (NILK-3801) κλ Bispecific Antibodies for Next Generation Immunotherapy of GPC3-Expressing Solid Cancers (APASL 2023)
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
IO biomarker
|
CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule) • GPC3 (Glypican 3)
|
GPC3 expression • GPC3 positive
|
NILK-2501 • NILK-3801 • theralizumab (TAB08)
over2years
Inhibition of Glypican-3 Cleavage Results in Reduced Cell Proliferation in a Liver Cancer Cell Line. (PubMed, J Surg Res)
GPC3 cleavage in hepatoblastoma (HB) has a role in cell proliferation with therapeutic potential, however furin inhibition is not an appropriate target for GPC3-expressing HB due to increased migration which may enhance metastatic potential.
Preclinical • Journal
|
GPC3 (Glypican 3) • FURIN (Furin, Paired Basic Amino Acid Cleaving Enzyme)
|
GPC3 expression • GPC3 positive