Table 1.
Principal clinical trials with immune checkpoint inhibitors targeting the PD-(L)1 pathway in monotherapy.
|
Pembrolizumab
|
Nivolumab
|
Atezolizumab
|
Durvalumab
|
Avelumab
|
|||||
|---|---|---|---|---|---|---|---|---|---|
| Keynote 0246 | Keynote 0105 | CheckMate 02623 | CheckMate 01721 | CheckMate 05722 | Birch (Cohort 1)24 | Oak7 | Study 1108 (Expansion cohort)11 | Javelin Solid Tumor25 (Expansion cohort) | |
| Phase | III | II/III | III | III | III | II | III | I/II | Ib |
| N (number of patients) | 305 (1:1) | 1034 (1:1:1) 345 pembrolizumab 2 mg/kg |
423 (1:1) | 272 (1:1) | 582 (1:1) | 659 139 1L (cohort 1) |
1225 (1:1) | 304 | 184 |
| Histology | All comers | All comers | All comers | Squamous cell | Nonsquamous cell | All comers | All comers | All comers | All comers |
| Line | 1 L | 2 L | 1 L | 2 L | 2 L | 1 L | 2 L | 1-2-3 L | 2 L |
| PD-L1 | >50% | >1% | >5% | – | – | >5% | – | >25% | – |
| Doses | 200 mg (flat dose) Q3w | 2 mg/kg 10 mg/kg Q3w |
3 mg/kg Q2w | 3 mg/kg Q2w | 3 mg/kg Q2w | 1200 mg flat dose Q3w | 1200 mg flat dose Q3w | 10 mg/kg | 10 mg/kg Q2w |
| ORR (ITT) | 44.8% (95% CI 36.8–56) | 18% (95% CI 14.1–22.5) | 26% (95% CI 20–33) | 20% (95% CI 14–28) | 19% (95% CI 15–24) | 25% (95% CI 18–33) | 14% (95% CI 11–17) | All: 25% (95% CI 18–32) 1 L: 29% (95% CI 17–43) 2L: 26% (95% CI 14–41) ⩾3 L 22% (95% CI 12–35) |
12% (95% CI 8–18%) |
| PFS | 10.3 (95% CI 6.7–NR) | 3.9 (95% CI 3.1–4.1) | 4.2 (95% CI 3–5.6) | 3.5 (95% CI 2.1–4.9) | 2.3 (95% CI 2.2–3.3) | 5.4 (95% 3–6.9) | 2.8 (95% CI 2.6–3) | NA | 2.9 (95% CI 2.1–3.4) |
| OS (ITT) | NR | 10.4 (95% CI 9.4–11.9) | 14.4 (95% CI 11.7–17.1) | 9.2 (95% CI 7.3–13.3) | 12.2 (95% CI 9.7–15) | 23.5 (95% CI 18.1–NE) | 13.8 (95% CI 11.8–15.7) | 1 L: No mature 2 L: 17.8 (95% CI 7.9–22.4) 3 L: 13 (95% CI 6–NA) |
8.4 (95% CI 7.3–10.6) |
| Duration of response | NR (range 1.9–14.5) | 2.0 (0.66–20.3) | 12.1 (95% CI 1.7–19.4) | 25.2 (95% CI 9.8–30.4) | 17.2 (95% CI 8.4–NR) | 9.8 (95% CI 5.6–NE) | 16.3 (95% CI 10–NE) | NA | NA |
| AEs G3/4 | 26.6% (G5 included) | 43% (G5 included) | 18% | 7% | 10% | 41% (G5 included) | 15% | 10 % | 13% |
1L, first line; 2L, second line; 3L, third line; AEs, adverse events; CI, confidence interval; ITT, intention to treat; NE, nonevaluable; NA, Not Available; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.