Table 3.
Clinical trials targeting various claudins.
| Clinical Trial ID | Phase | Drug | Target | Cancer | Results |
|---|---|---|---|---|---|
| MONO trial NCT01197885 [12] |
IIa | zolbetuximab as a single agent | CLDN18.2 | Advanced relapsed or refractory G/GEJ or esophageal adenocarcinomas | PR = 9% |
| FAST trial NCT01630083 [189] |
II | epirubicin + oxaliplatin + capecitabine (EOC)+ zolbetuximab vs. EOC + placebo | CLDN18.2 | G/GEJ and esophageal adenocarcinomas | DCR 76.2% |
| NCT03874897 [190] | I | CLDN18.2 CAR-T | CLDN18.2 | Previously treated gastrointestinal cancer | ORR 48.6% DCR 73.0% |
| Lordick et al., NCT01671774 [191] | I | zolbetuximab alone or in combination with ZA or with ZA plus IL-2 | CLDN18.2 | Relapsed or refractory G/GEJ or esophageal adenocarcinomas | PFS of 37.3 weeks with zolbetuximab alone vs. 7.1 to 12.7 weeks in other Rx arms. OS of 60.9 weeks in zolbetuximab + ZA + IL-2 arm, numerically higher than other arms |
| ILUSTRO trial [192] | II | zolbetuximab monotherapy (in ≥third line) vs. zolbetuximab + mFOLFOX6 (in first line) vs. zolbetuximab + pembrolizumab (in ≥third line) | CLDN18.2 | Advanced /metastatic G/GEJ adenocarcinoma | ORR 71.4% in zolbetuximab + mFOLFOX group, but % in the other 2 cohorts |
| SPOTLIGHT trial NCT03504397 [193] |
III | mFOLFOX6 + zolbetuximab vs. mFOLFOX6 + placebo | CLDN18.2 | Locally advanced or metastatic HER-2-negative G/GEJ adenocarcinoma | PFS 10.61 vs. 8.67 months in Rx vs. placebo group. HR 0.75, p = 0.0066 |
| GLOW trial NCT03653507 [194] |
III | CAPOX + zolbetuximab vs. CAPOX + placebo | CLDN18.2 | Locally advanced or metastatic HER-2-negative G/GEJ adenocarcinoma | PFS 8.21 vs. 6.80 months in Rx vs. placebo group. HR 0.687, p = 0.0007 |
| McDermott et al. [13] | Preclinical trial | humanized anti-CLDN6 monoclonal antibody coupled with monomethyl auristatin E (MMAE) via a cleavable linker | CLDN6 | CLDN6 high-expressing cell line and xenograft models | |
| BNT211-01 trial NCT04503278 [195] | I/II | (CAR)-T with or without a CAR-T cell-amplifying RNA vaccine (CARVac) | CLDN6 | Relapsed/refractory CLDN6-positive solid tumors | Unconfirmed ORR 33% (57% inpatient with germ cell tumors) |
| Adra et al. NCT03760081 [196] | II | ASP1650: a chimeric-mouse/human-IgG1 antibody | CLDN6 | Testicular germ cell tumors with average of 3 prior lines of therapy | The study was stopped at the end of Simon Stage-I due to a lack of efficacy |
ORR: overall response rate; DCR: disease control rate; G/GEJ: gastric/gastroesophageal junction; PFS: progression-free survival; FOLFOX: 5-fluorouracil + folic acid + oxaliplatin; CAPOX: capecitabine + oxaliplatin; PR: partial response; ZA: zoledronic acid.