Table 1.
Summary of clinical trials for cancer immunotherapy targeting GPC3.
| Trial | ID | References | Key inclusion criteria | Primary endpoint | Results |
|---|---|---|---|---|---|
| OUR CLINICAL TRIALS | |||||
| Phase I clinical study of GPC3 peptide vaccine in patients with advanced HCC | UMIN 000001395 | Sawada et al. (30) | Advanced HCC patient | (1) Adverse effects of GPC3 vaccine | GPC3 vaccination was well-tolerated; the vaccine induced a GPC3-specific CTL response in 30/33 patients (91%) |
| (2) GPC3-specific immune responses to GPC3 vaccine | |||||
| Clinical study evaluating immunological efficacy of GPC3 peptide vaccine in patients with advanced HCC | UMIN 000005093 | Tsuchiya et al. (34) | Advanced HCC patient | Increased percentage of GPC3 peptide-specific CD8-positive T lymphocytes in blood and tumor | After vaccination, the number of GPC3 peptide-specific CTLs in PBMC was increased in 9 of 11 patients; tumor biopsy specimens obtained from three patients post-vaccination revealed CTL infiltration |
| Phase II study of GPC3 peptide vaccine as adjuvant treatment for HCC after surgical resection or RFA | UMIN 000002614 | Sawada et al. (31) | (1) Diagnosed as initial HCC | 1- and 2-year recurrence rate | 1- and 2-year recurrence rates were 24.4 and 53.7%, respectively; the primary endpoint was not reached |
| (2) Subjects who underwent potentially curative surgical resection or RFA for treatment of HCC | |||||
| Phase II study of GPC3 peptide vaccine for treatment of OCCC | UMIN 000003696 | Suzuki et al. (32) | Advanced OCCC patient | DCR at 6 months | DCR at 6 months was 9.4% (3/32) |
| Phase I study of GPC3 peptide vaccine for pediatric patients with refractory tumors | UMIN 000006357 | Tsuchiya et al. (33) | (1) Patients with refractory, recurrent, or progressive status (progressive group) | Incidence of DLT | No DLT or dose-specific adverse events were observed |
| (2) Patients in remission without chance of cure (remission group) | |||||
| (3) Patients in partial remission or with stable disease (partial remission group) | |||||
| OTHER CLINICAL TRIALS | |||||
| First-in-man phase I study of GC33, a novel recombinant humanized antibody against glypican-3, in patients with advanced hepatocellular carcinoma | NCT 00746317 | Zhu et al. (36) | Patients with measurable, histologically demonstrated advanced HCC | Maximum tolerated dose was not reached as there was no DLT up to the highest planned dose level. Median TTP was 26.0 and 7.1 weeks in the high and low GPC3 expression groups, respectively | |
| Japanese phase I study of GC33, a humanized antibody against glypican-3 for advanced hepatocellular carcinoma | JapicCTI 101255 | Ikeda et al. (37) | Japanese patients with advanced HCC | No DLT observed in any patient up to the highest planned dose; 7/13 patients showed SD, 6/13 showed PD, and 3/13 showed long-term SD >5 months | |
CTL, cytotoxic T lymphocyte; DCR, disease control rate; DLT, dose-limiting toxicity; GPC3, glypican-3; HCC, hepatocellular carcinoma; OCCC, ovarian clear cell carcinoma; PBMC, peripheral blood mononuclear cell; PD, progressive disease; RFA, radiofrequency ablation; SD, stable disease; TTP, time to progression.