Table 1.
Completed clinical trial of PD-1/PD-L1 inhibitors monotherapy in recurrent and/or metastatic (R/M) NPC.
| Trial | Design | Population | Previous lines | Treatment and dosage | ORR (%) | DCR (%) | Median PFS (95% CI), months | Median OS (95% CI), months | DOR (95% CI), months | Grade ⩾ 3 TRAEs (%) | The most common Grade ⩾ 3 TRAEs |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CAPTAIN | Phase I | 91, Asian (100%) | 37.0% patients ⩾ 3 | Camrelizumab: anti-PD-1 IgG4 mAb bridging dose of 200 mg every 2 weeks |
34.0 | 59.0 | 5.6 (3.3–7.9) | NA | NR (6.3–NR) | 16.0 | Anemia (2.0%); ALT elevation (2.0%); AST elevation (2.0%); bilirubin elevation (2.0%) |
| NCI-9742 | Phase II | 45, Asian (82.2%) | 61.0% patients ⩾ 3 | Nivolumab: anti-PD-1 IgG4 mAb 3 mg/kg every 2 weeks |
20.5 | 54.5 | 2.8 (1.8–7.4) | 17.1 (10.9–NR) | NA | 22.0 | Hepatitis, diarrhea, fatigue, hyponatremia ALT elevation, neutropenia |
| a KEYNOTE-028 | Phase Ib | 27, Asian (63%) | 70.4% patients ⩾ 3 | Pembrolizumab: anti-PD-1 IgG4 mAb 10 mg/kg every 2 weeks |
25.9 | 37.0 | 3.7 (2.1–13.4) | 16.5 (10.1–NR) | 17.1 (4.8–22.1) | 29.0 | Hepatitis (7.4%); pneumonitis (7.4%) |
| POLARIS-02 | Phase II | 190, Asian (100%) | 48.4% patients ⩾ 2 | Toripalimab: anti-PD-1 IgG4 mAb 3 mg/kg once every 2 weeks |
20.5 | 40.0 | 1.9 (1.8–3.5) | 17.4 (11.7–22.9) | 12.8 (9.4–NR) | 14.0 | Anemia (1.1%); Asthenia (1.1%) Neutropenia (0.5%) |
| CheckMate 358 | Phase I/II | 24, European (88%) | All patients ⩽ 2 79.2% patients ⩾ 1 |
Nivolumab: anti-PD-1 IgG4 mAb 240 mg every 2 weeks |
20.8 | 45.8 | 2.4 (1.5–NR) | NR | NR | 8.3 | NA |
| NCT03866967 | Phase I | 130 were included, 111 in FAS, Asian (100%) | All patients ⩾ 2 | Penpulimab: anti-PD-1 IgG4 mAb with less binding to FcγR; 240 mg every 2 weeks |
29.7 | 49.5 | 3.7 (1.9–6.6) | 18.6 (14.1–NR) | NR | 8.5 | Hepatic function abnormal (2.3%); rash (2.3%) |
| CTR20160872 | Phase I/II | 300 patients with solid tumor including 21 R/M NPCs | NA | Tislelizumab: anti-PD-1 IgG4 mAb with less binding to FcγR; 200 mg every 3 weeks | 43.0 | 86.0 | 4.0 (2.1–8.1) | NA | 8.3 (3.9–NR) | 40.0 | GGT elevation (4%); Anemia (3.0%); AST elevation (3.0%); ALT elevation (3.0%) |
| b NCT02605967 | Phase II | 113 (2:1) in spartalizumab arm versus CT arm | All patients ⩾ 2 | Spartalizumab: anti-PD-1 IgG4 mAb 400 mg every 4 weeks, CT decided by investigators |
17.1 versus 35.0 | 35.0 versus 28.0 | 1.9 versus 6.6 | 25.2 versus 15.5 | 10.2 versus 5.7 | 18.4 versus 40.5 | NA |
| b KEYNOTE-122 | Phase III | 233 (1:1) in pembrolizumab arm versus CT arm |
All patients ⩾ 2 | Pembrolizumab: anti-PD-1 IgG4 mAb 200 mg every 3 weeks, CT decided by investigators |
21.4 versus 23.3 | 50.4 versus 63.8 | 4.1 versus 5.5 | 17.2 versus 15.3 | 12.0 versus 13.1 | 10.3 versus 43.8 | NA |
| NCT02825940 | Phase I | 20, Asian (100%) | NA | Atezolizumab: anti-PD-L1 IgG4 mAb 1200 mg every 3 weeks |
10.0 | 65.0 | NA | NA | NA | NA | Hyponatremia (5%); lipase increased (3%); aspartate aminotransferase (3%) |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; CT, chemotherapy; DCR, disease control rate; DOR, duration of response; GGT, Gamma-glutamyl transferase; mAb, monoclonal antibody; N/A, not available; NPC, nasopharyngeal carcinoma; NR, not reached; ORR, objective response rate; OS, overall survival; PD-1, programmed death-1; PD-L1, programmed death ligand-1; PFS, progression-free survival; R/M, recurrence and/or metastatic; TRAE, treatment-related adverse effect; FAS, full analysis set.
In the study of KEYNOTE-028, all R/M NPC patients had PD-L1 expression in 1% or more of tumor cells or tumor-infiltrating lymphocytes.
In the study of spartalizumab and KEYNOTE-122, the data of efficacy and safety are shown as anti-PD-1 antibody arm versus CT arm.