1. Summarized data from reported phase II/III clinical studies.
| Clinical trial name | Clinicaltrial.gov ID | Phase | Settings | Patients | Treatment | Efficacy results | Safety results |
| 1L, first-line; 2L, second-line; 3L, third-line; Mn, maintenance; GC, gastric cancer; GEJC, gastroesophageal junction cancer; PD-L1, programmed death ligand 1; HER2, human epidermal growth factor receptor 2; NIV, nivolumab; PEM, pembrolizumab; IPI, ipilimumab; CIS, cisplatin; 5-FU, 5-fluorouracil; CAPE, capecitabine; OX, oxaliplatin; ADX, andecaliximab; BSC, best supportive care; ORR, objective response rate; mPFS, median progression-free survival; mOS, median overall survival; TRAEs, treatment related adverse effects. | |||||||
| CheckMate-032 (30) | NCT01928394 | I/II | 2L or 3L+ | GC/GEJC (PD-L1 unselected): N1I3: 48 N3I1: 52 N3: 59 | N3: NIV 3 mg/kg, q2w; N1I3: NIV 1 mg/kg + IPI 3 mg/kg, q3w; N3I1: NIV 3 mg/kg + IPI 1 mg/kg, q3w | ORR: N1I3, 24%; N3I1, 8%; N3, 12%
mPFS: N1I3, 1.4 months; N3I1, 1.6 months; N3, 1.4 months mOS: N1I3, 6.9 months; N3I1, 4.8 months; N3, 6.2 months |
Grade 3−4 TRAEs: N1I3 47%; N3I1 27%; N3 17% |
| KEYNOTE-059 cohort 1 (21) | NCT02335411 | II | 3L+ | GC/GEJC (PD-L1 unselected): 259 | PEM 200 mg, q3w | ORR: 12% (PD-L1 + 16%; PD-L1− 6%)
mPFS: 2.0 months mOS: 5.5 months |
Grade ≥3 TRAEs: 18% |
| KEYNOTE-059 cohort 2 (40) | NCT02335411 | II | 1L | GC/GEJC (PD-L1 unselected, HER2−): 25 | PEM 200 mg, q3w + CIS + 5-FU or CAPE | ORR: 60% (PD-L1+ 73%; PD-L1− 38%)
mPFS: 6.6 months mOS: 13.8 months |
Grade ≥3 TRAEs: 76% |
| KEYNOTE-059 cohort 3 (40) | NCT02335411 | II | 1L | GC/GEJC (PD-L1+, HER2-): 31 | PEM 200 mg, q3w | ORR: 26%
mPFS: 3.3 months mOS: 20.7 months |
Grade ≥3 TRAEs: 23% |
| N/A cohort 1 (23) | NCT02915432 | I/II | 2L or 3L+ | GC/GEJC (PD-L1 unselected): 58 | Toripalimab 3 mg/kg, q2w | ORR: 12%
mPFS: 1.9 months mOS: 4.8 months |
Grade 3−4 TRAEs: 22% |
| N/A cohort 2 (23) | NCT02915432 | I/II | 1L | GC/GEJC (PD-L1 unselected): 18 | Toripalimab 360 mg, q3w + OX + CAPE | ORR: 67%
mPFS: 5.8 months mOS: not reached |
Grade ≥3 TRAEs: 39% |
| N/A (31) | NCT02340975 | I/II | 2L or 3L | GC/GEJC (PD-L1 unselected, HER2−): 2L-D+T: 27; 2L-D: 24; 2L-T: 12; 3L-D+T: 25; 2L/3L-D+T INF-γ+: 19 | 2L-D+T: durvalumab 20 mg/kg + tremelimumab 1 mg/kg, q4w
2L-D: durvalumab 10 mg/kg, q2w 2L-T: tremelimumab 10 mg/kg, q4w → q12w 3L-D+T: durvalumab 20 mg/kg + tremelimumab 1 mg/kg, q4w → durvalumab 10 mg/kg, q2w 2L/3L-D+T INF-γ+: durvalumab 20 mg/kg + tremelimumab 1 mg/kg, q4w → durvalumab 10 mg/kg, q2w |
ORR: 2L-D+T, 7.4%; 2L-D, 0%; 2L-T, 8.3%; 3L-D+T, 4%; 2L/3L-D+T INF-γ+, 16%
mPFS: 2L-D+T, 1.8 months; 2L-D, 1.6 months; 2L-T, 1.7 months; 3L-D+T, 1.8 months; 2L/3L-D+T INF-γ+, 1.8 months mOS: 2L-D+T, 9.2 months; 2L-D, 3.4 months; 2L-T, 7.7 months; 3L-D+T, 10.6 months; 2L/3L-D+T INF-γ+, 7.0 months |
Grade ≥3 TRAEs: 2L-D+T 17%; 2L-D 4%; 2L-T 42%; 3L-D+T 16%; 2L/3L-D+T INF-γ+ 11% |
| NivoRam (34) | NCT02999295 | I/II | 2L | GC (PD-L1 unselected): 46 | NIV 3mg/kg, q2w + ramucirumab 8 mg/kg, q2w | ORR: 27%
mPFS: 2.9 months mOS: 9.0 months |
Grade ≥3 TRAEs: 28% |
| MEDIOLA (36) | NCT02734004 | I/II | 2L or 3L+ | GC (PD-L1 unselected): 39 | Olaparib 300 mg → olaparib + durvalumab 1,500 mg, q4w | ORR: 10%
mPFS; not reached mOS: not reached |
Grade ≥3 TRAEs: 57% |
| N/A (38) | NCT02864381 | II | 2L or 3L+ | GC/GEJC (PD-L1 unselected): 144 | Arm1: ADX 800 mg + NIV 3 mg/kg, q2w
Arm2: NIV 3 mg/kg, q2w |
ORR: arm1, 11%; arm2, 7%
mPFS: arm1, 1.8 months; arm2, 7.2 months mOS: arm1, 1.9 months; arm2, 5.9 months |
Grade ≥3 TRAEs: not reported |
| N/A (39) | NCT02689284 | I/II | 2L | GC/GEJC (PD-L1 unselected, HER2+): 66 | Margetuximab 15 mg/kg + PEM 200 mg, q3w | ORR: 41%
mPFS: 5.5 months mOS: not reached |
Grade ≥3 TRAEs: 18% |
| CA184-162 (42) | NCT01585987 | II | 1L Mn | GC/GEJC (PD-L1 unselected): 143 | Arm1: IPI 10 mg/kg, q3w → 10 mg/kg, q12w
Arm2: BSC |
ORR: arm1, 1.8%; arm2, 7.0%
mPFS: arm1, 2.9 months; arm2, 4.9 months mOS: arm1, 12.7 months; arm2, 12.1 months |
Grade ≥3 TRAEs: Ipili 23%; BSC 9% |
| ATTRACTION-4 (45) | NCT02746796 | II | 1L | GC/GEJC (PD-L1 unselected, HER2−): 38 | Arm1: NIV 360 mg, q3w + S-1 + OX (SOX)
Arm2: NIV 360 mg, q3w + CAPE + OX (CapeOX) |
ORR: arm1, 57%; arm2, 77%
mPFS: arm1, 9.7 months; arm2, 10.6 months mOS: not reached |
Grade ≥3 TRAEs: arm1 57%; arm2 67% |
| KEYNOTE-659 (46) | NCT03382600 | II | 1L | GC/GEJC (PD-L1+, HER2−): 54 | Cohort1: PEM 200 mg, q3w + S-1 + OX (SOX) | ORR: 72%
mPFS: 9.4 months mOS: not reached |
Grade ≥3 TRAEs: 57% |
| N/A (48) | NCT03615326 | II | 1L | GC/GEJC (PD-L1 unselected, HER2+): 37 | PEM 200 mg, q3w + trastuzumab 6 mg/kg + OX + CAPE | ORR: 81%
mPFS: 14.2 months mOS: not reached |
Grade ≥3 TRAEs: not reported |
| ATTRACTION-2
(22) |
NCT02267343 | III | 3L+ | GC/GEJC (PD-L1 unselected): 493 | Arm1: NIV 3 mg/kg, q2w
Arm2: placebo |
ORR: arm1, 11%; arm2, 0%
mPFS: arm1, 1.6 months; arm2, 1.5 months mOS: arm1, 5.3 months; arm2, 4.1 months |
Grade 3−4 TRAEs: arm1 10%; arm2 4% |
| KEYNOTE-061
(25) |
NCT02370498 | III | 2L | GC/GEJC (PD-L1+): 395 | Arm1: PEM 200 mg, q3w
Arm2: paclitaxel |
ORR: arm1, 16%; arm2, 14%
mPFS: arm1, 1.5 months; arm2, 4.1 months mOS: arm1, 9.1 months; arm2, 8.3 months |
Grade 3−5 TRAEs: arm1 14%; arm2 35% |
| GASTRIC-300
(28) |
NCT02625623 | III | 3L | GC/GEJC (PD-L1+): 371 | Arm1: 10 mg/kg, q2w
Arm2: physician’s choice of chemotherapy |
ORR: arm1, 2.2%; arm2, 4.3%
mPFS; arm1, 1.4months; arm2, 2.7 months mOS: arm1, 4.6 months; arm2, 5.0 months |
Grade ≥3 TRAEs: arm1 9.2%; arm2 32% |
| GASTRIC-100
(43) |
NCT02625610 | III | 1L Mn | GC/GEJC (PD-L1 unselected, HER2−): 499 | Arm1: avelumab 10 mg/kg, q2w
Arm2: continued chemotherapy |
ORR: arm1, 13%; arm2, 14%
mPFS: not reported mOS: not reported |
Grade ≥3 TRAEs: arm1 13%; arm2 33% |
| KEYNOTE-062
(41) |
NCT02494583 | III | 1L | GC/GEJC (PD-L1+, HER2−): 763 | P: PEM 200 mg, q3w
P+C: PEM 200 mg, q3w + CIS + 5-FU or CAPE C: placebo + CIS + 5-FU or CAPE |
ORR: P, 15%; P+C, 49%; C, 37%
mPFS; P, 2.0 months; P+C, 6.9 months; C, 6.4 months mOS: P, 10.6 months; P+C, 12.5 months; C, 11.1 months |
Grade 3−5 TRAEs: P 17%; P+C 73%; C 69% |