Table 5.
Completed clinical trials of EBV-CTLs in NPC.
| Ref. | Status | Design | Population | Disease status | Therapy lines | Treatment | Efficacy | Grade ⩾ 3 TRAEs |
|---|---|---|---|---|---|---|---|---|
| (Chua et al.)87 | Completed | Pilot | 4 | R/M EBV (+) NPC | ⩾2 | Autologous EBV-CTLs | 3/4: EBV burden decrease; 3/4: die of PD (9–21 months after EBV-CTLs) | None |
| (Comoli et al.)88 | Completed | Preliminary | 1 | Relapsed EBV (+) NPC | ⩾2 | EBV-specific CTLs | SD | None |
| (Comoli et al.)89 | Completed | Phase I | 10 | Stage IV EBV (+) NPC | ⩾2 | LCL-stimulated CTL with low-dose IL-2 | 2/10: PR; 4/10: SD; 4/10: PD | None |
| (Straathof et al.)90 | Completed | Phase I | 10 | Stage III/IV EBV (+) NPC in remission or with R/R history |
⩾2 | EBV-specific CTLs | Four pts with previous remission: DFS: 19–27 months; 6 pts with previous R/R NPC: 2/6: CR; 1/6: PR; 1/6: SD; 2/6: no response |
None |
| (Louis et al. 2009)91 | Completed | Phase I | 8 | EBV (+) poorly differentiated or undifferentiated NPC (WHO type II/III) | ⩾2 | CTL following anti-CD45 mAb administration | 1/8: CR; 2/8: SD; 5/8: PD | None |
| (Louis et al.)92 | Completed | Phase I/II | 23 | R/R EBV (+) NPC | ⩾2 | EBV-specific CTLs | Eight pts in remission: 6/8: PFS: 17–75 months; 2/8: PD 15 pts with previous R/R NPC:5/15: CR; 2/15: PR; 3/15: SD; 5/15: PD |
None |
| (Secondino et al.)93 | Completed | Phase II | 11 | Stage IV, EBV-LMP1- and EBER-positive NPC | ⩾2 | CTL following cyclophosphamide and fludarabine CT | 2/11: PR; 1/11: minor response; 3/11: SD; 5/11: PD | 4/11: G3 neutropenia |
| Smith et al. 86 | Completed | Phase II | 29a | 9 pts with no or minimal residual disease (N/MRD) 20 pts with active recurrent/metastatic disease (ARMD) |
⩾2 | AdE1-LMPpoly vector-based CTL | ARMD:12/20: SD; 8/20: PD; N/MRD:6/9: maintain response; 3/9: PD All: mPFS: 5.5 months; mOS: 38.1 months |
2/29: G3 lung abscess |
| Chia et al. 94 | Completed | Phase II | 38b | Metastatic/locoregional EBV (+) NPC | 1 | EBV-CTL following GC CT | 3/38: CR; 22/38: PR; 11/38: SD; 1/38: PD; 1/38: N/A; 3-year OS: 37.1% | None |
| (Lutzky et al.)95 | Completed | Case report | 1 | Refractory metastatic EBV (+) NPC | ⩾2 | EBV-specific CTLs | PR | None |
| (Huang et al.)96 | Completed | Phase I/II | 21c | R/M EBV (+) NPC | ⩾2 | EBV-specific CTLs | 1/21: CR; 2/21: SD; 18/21: PD; mPFS: 2.2 months; mOS: 16.7 months | None |
CR, complete response; CT, chemotherapy; CTL, cytotoxic T-cell; DCR, disease control rate; DFS, disease-free survival; EBV, Epstein–Barr virus; GC, gemcitabine and carboplatin; LMP, latent membrane protein; N/A, not available; N/MRD, no or minimal residual disease; NPC, nasopharyngeal carcinoma; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; R/M, recurrent/metastatic; R/R, refractory or relapsed; Ref., reference; SD, stable disease; WHO, World Health Organization; IL-2, interleukin-2.
29a:1 Patient of 30 pts died after single administration due to lung abscess.
38b: 35 of 38 pts received GC and EBV-CTL.
21c: 21 of 28 enrolled pts received EBV-CTL.