Univariate analysis
| Demographics and clinical characteristics in phase II (n=49) | ||||||
| Median PFS (central) (95% CI) | PFS at 6 months, % (95% CI) | P value | Median OS (95% CI) | OS at 18 months, % (95% CI) | P value | |
| Age | 0.4 | 0.55 | ||||
| 0–44 | 4.5 (1.8 to 7.1) | 45 (36 to 55) | NR | 75 (65 to 84) | ||
| >44 | 6.5 (2.2 to 10.8) | 52 (41 to 63) | 24.1 (18.6 to 29.7) | 61 (51 to 71) | ||
| MFI (years) | 0.59 | 0.97 | ||||
| 0–1 | 4.5 (2.6 to 6.3) | 43 (33 to 52) | 24.1 (NA) | 66 (56 to 76) | ||
| >1 | 6.1 (0 to 14.6) | 54 (44 to 65) | NR | 68 (58 to 78) | ||
| Baseline ECOG | 0.2 | 0.098 | ||||
| 0 | 7.3 (4.2 to 10.4) | 56 (46 to 66) | NR | 80 (72 to 88) | ||
| 1 | 4.1 (3 to 5.2) | 40 (29 to 50) | 22.5 (8.8 to 36.2) | 51 (39 to 63) | ||
| Baseline extension | 0.9 | 0.22 | ||||
| Metastatic | 6.1 (2.6 to 9.6) | 50 (43 to 58) | 24.1 (19.5 to 28.8) | 63 (56 to 71) | ||
| Locally advanced | 3.8 (1.3 to 6.2) | 25 (2 to 48) | NR | 100 (NA) | ||
| Previous lines | 0.28 | 0.096 | ||||
| 0–1 | 5.6 (0.8 to 10.3) | 49 (39 to 59) | NR | 76 (67 to 86) | ||
| >1 | 4.1 (0.6 to 7.7) | 47 (37 to 58) | 21 (6.5 to 35.6) | 55 (44 to 66) | ||
| Previous antiangiogenic | 0.27 | 0.71 | ||||
| No | 4.4 (2.6 to 6.2) | 41 (33 to 49) | 24.1 (19.7 to 28.6) | 65 (57 to 73) | ||
| Yes | 15.5 (4.3 to 26.7) | 73 (59 to 86) | NR | 72 (58 to 86) | ||
| Central RECIST response | 0.005 | 0.01 | ||||
| CR/PR | 11.7 (10.9 to 12.4) | 100 | NR | 100 | ||
| SD | 3.7 (1.6 to 5.9) | 39 | NR | 75 | ||
| PD | 0 | 0 | 3.9 (0 to 11.6) | 44 | ||
| Central Choi response | 0.005 | 0.97 | ||||
| PR | 5.6 (0.6 to 10.6) | 48 | 22.3 (19.3 to 25.3) | 68 | ||
| SD | 4.4 (0 to 17.8) | 50 | NR | 80 | ||
| PD | 0 | 0 | NR | 67 | ||
| RNA expression genes from phase Ib and II (n=28)* | ||||||
| PDGFD† | 0.005 | 0.005 | ||||
| 0–4.9 | 3.5 (1.7 to 5.2) | 17 (6 to 27) | 9.8 (7.2 to 12.5) | 25 (12 to 37) | ||
| >4.9 | 11.5 (3.9 to 19.1) | 74 (63 to 85) | NR | 93 (87 to 100) | ||
| IL16† | 0.005 | 0.022 | ||||
| 0–6.1 | 4 (2.5 to 5.5) | 24 (14 to 35) | 13.9 (0.6 to 27.3) | 47 (35 to 59) | ||
| >6.1 | 13.5 (8.2 to 18.8) | 90 (80 to 99) | NR | 90 (80 to 99) | ||
| TAL1† | 0.01 | 0.007 | ||||
| 0–3.5 | 3 (0.2 to 5.7) | 12 (1 to 24) | 8.4 (0 to 18.7) | 25 (10 to 40) | ||
| >3.5 | 7.5 (3.8 to 11.1) | 64 (53 to 75) | NR | 79 (70 to 88) | ||
| IL23A† | 0.27 | 0.018 | ||||
| 0–4.1 | 5.2 (2.1 to 8.2) | 38 (25 to 52) | 12.7 (6.2 to 19.2) | 38 (25 to 52) | ||
| >4.1 | 7.5 (2 to 12.9) | 58 (45 to 71) | NR | 86 (76 to 95) | ||
| TNFSF13B† | 0.017 | 0.007 | ||||
| 0–5.3 | 3 (0.1 to 5.9) | 10 (0 to 19) | 9.8 (0 to 21.4) | 30 (15 to 44) | ||
| >5.3 | 7.5 (4.2 to 10.7) | 71 (60 to 82) | NR | 82 (73 to 92) | ||
| CD276† | 0.005 | 0.005 | ||||
| 0–8.4 | 9.6 (4.8 to 14.4) | 67 (56 to 78) | NR | 83 (74 to 92) | ||
| >8.4 | 3 (0.5 to 5.4) | 11 (1 to 22) | 8.4 (0 to 17.5) | 22 (8 to 36) | ||
| PDCD1 (PD-1)† | 0.007 | 0.17 | ||||
| 0–4.5 | 4.1 (3.2 to 5) | 32 (21 to 42) | 21.1 (7.4 to 34.6) | 53 (41 to 64) | ||
| >4.5 | 15.5 (12.9 to 18.1) | 89 (78 to 99) | NR | 87 (76 to 99) | ||
| CD274 (PD-L1)† | 0.19 | 0.009 | ||||
| 0–4.9 | 4.1 (2.1 to 6.1) | 33 (20 to 47) | 9.9 (5.1 to 14.8) | 33 (20 to 47) | ||
| >4.9 | 7.5 (0 to 16.3) | 61 (48 to 73) | NR | 87 (78 to 96) | ||
| Hierarchical clustering‡ | 0.25 | 0.021 | ||||
| Group 1 | 4.1 (1.8 to 6.5) | 27 | 12.7 (6.7 to 18.7) | 27 | ||
| Group 2 | 7.5 (6.6 to 8.3) | 59 | NR | 59 | ||
*Samples with sufficient material for direct transcriptomics.
†Genes were categorized using ROC curves for their impact on progression-free survival and overall survival.
‡Taking into account the genes with impact on overall survival.
CR, complete response; ECOG, Eastern Cooperative Oncology Group; MFI, metastasis-free interval; NR, not-reached; OS, overall survival; PD, progressive disease; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; ROC, receiver operating characteristic curve; SD, stable disease.