Table 3.
List of major completed phase II-III trials with immune checkpoint inhibitors in metastatic gastric cancer.
| Study Name [Reference] |
Agents (Target) | Country | Phase | Line | PD-L1 Status | Treatment Arms | N | Primary Endpoints | OS | PFS | RR (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Keynote-062 [62] |
Pembrolizumab (PD-1) | Global | III | 1° | CPS ≥ 1% | cisplatin + 5-fluorouracil/capecitabine (CT) | 250 | OS, PFS | Non-inferiority: 10.6 (I) vs. 11 (CT) Superiority: 12.5 (CT + I) vs. 11.1 (CT) |
Superiority: 6.9 (CT + I) vs. 6.4 (CT) | 48.6 (CT + I) 37.2 (CT) |
| cisplatin + 5-fluorouracil /capecitabine + pembrolizumab (CT + I) | 257 | ||||||||||
| pembrolizumab (I) | 256 | ||||||||||
| Checkmate-649 (preliminary results) [98] |
Nivolumab (PD-1) Ipilimumab (CTLA-4) |
Global | III | 1° | Unselected | nivolumab + ipilimumab | OS, PFS | CPS ≥ 5%: 7.7 6.1 |
NR | ||
| Xelox/Folfox | 482 | 14 | |||||||||
| Xelox/Folfox + nivolumab | 473 | 11.3 | |||||||||
| Attraction-4 (preliminary results) [99] |
Nivolumab (PD-1) | Asian | III | 1° | Unselected | Nivolumab + S-1 oxaliplatin/Xelox | 362 | PFS, OS | 17.5 | 10.5 | NR |
| S-1 oxaliplatin/Xelox | 362 | 17.2 | 8.3 | ||||||||
| Janjigian et al. [100] |
Pembrolizumab (PD-1) | Global | II | 1° | Unselected | Xelox/Folfox/cisplatin plus 5-fluorouracil+ trastuzumab+ pembrolizumab | 37 | PFS at 6 months | 27.3 | 13 | 100 |
| Javelin Gastric 100 [101] |
Avelumab (PD-L1) | Global | III | 1°mantainance | Unselected | Avelumab | 249 | OS | 10.4 | 3.2 | 13.3 |
| Folfox/Xelox | 250 | 10.9 | 4.4 | 14.4 | |||||||
| Keynote-061 [102] |
Pembrolizumab (PD-1) | Global | III | 2° | CPS ≥ 1% | Pembrolizumab | 196 | PFS, OS | 9.1 | 1.5 | 16 |
| Paclitaxel | 199 | 8.3 | 4.1 | 14 | |||||||
| Keynote-059 (cohort 1) [54] |
Pembrolizumab (PD-1) | Global | II | ≥3° | Unselected (57.1% CPS ≥ 1%) |
Pembrolizumab | 259 | RR | 5.6 | 2 | 11.6 |
| Attraction-02 (ONO-4538-12) [103] |
Nivolumab (PD-1) | Asian | III | ≥3° | Unselected | Nivolumab | 330 | OS | 7.5 | 1.6 | 11 |
| Placebo | 163 | 5.1 | 1.5 | 20 | |||||||
| Checkmate-032 [104] |
Nivolumab (PD-1) Ipilimumab (CTLA-4) |
Western | I-II | ≥3° | Unselected | Nivolumab | 59 | RR | 6.2 | 1.4 | 12 |
| Nivolumab1/Ipilimumab3 * | 49 | 6.9 | 1.6 | 24 | |||||||
| Nivolumab3/Ipilimumab1 ** | 52 | 4.8 | 1.6 | 8 | |||||||
| Javelin Gastric 300 [105] | Avelumab (PD-L1) | Global | III | 3° | TPS ≥ 1% | Avelumab | 272 | OS | 4.6 | 1.4 | 4.6 |
| Physician’s choice ‡ | 133 | 5 | 2.7 | 5 |
* Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks. ** Nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks. ‡ Paclitaxel 80 mg/m2 on days 1, 8 and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle. Legend: N: patient number; NR: not reported; CPS: PD-L1 combined positive score; TPS: PD-L1 tumor proportion score; PD-1: programmed cell death protein-1; CTLA-4: Cytotoxic T-Lymphocyte Antigen 4; PD-L1: programmed cell death protein-ligand 1; OS: overall survival (months); PFS: progression-free survival (months); RR: response rate; NR: not reported.