Table 2.
Summary of clinical trials on tyrosine-kinase inhibitors (TKIs) targeting ROS-1 in patients with ROS-1-positive non-small-cell lung cancers.
| TKI | Clinical Trial | Phase | N | ORR (95% CI) | mPFS (mo) (95% CI) | mOS (mo) [95% CI] | 1-Year OS | Grade-3/4 Adverse Events (%) |
|---|---|---|---|---|---|---|---|---|
| Crizotinib | PROFILE 1001 | Prospective I/II | 53 | 72% (58–83) | 19 (15–39) | 51 (29–NR) | 36% | |
| EUROS-1 | Retrospective | 31 | 80% | 9 | — | — | — | |
| AcSé | Prospective I/II | 36 | 47% (30–65) | 6 (4–9) | 17 (9–33) | — | — | |
| EUCROSS | Prospective II | 34 | 70% (51–85) | 20 [8–NR] | Not reached | 83% | 24% | |
| METROS | Prospective II | 26 | 65% (44–82) | 23 (15–30) | NR | — | 27% | |
| East Asian | Prospective II | 127 | 72% (63–79) | 16 (13–24) | 33 | 83% | 25% | |
| Shanghai | Retrospective | 30 | 87% (73–97) | 18 (6–30) | NR | 81% | 23% | |
| Beijing | Retrospective | 56 | 84% | 15 (11–19) | NR | — | — | |
| China | Retrospective | 168 | 86% | 18 | — | — | — | |
| Entrectinib | ALKA-372-001/STRATRK-1/STARTRK-2 | Prospective I/II | 161 | 67% (59–74) | 16 (11–21) | NR | 81% | 31% a |
| Lorlatinib | NCT01970865 | Prospective I/II | 69 | 62% (38–82) b 35% (21–52) c |
21 (4–32) b 9 (5–15) c |
— | — | 43% |
| Ceretinib | NCT01964157 | Prospective II | 32 | 62% (45–77) | 9 (0–22) d 19 (1–37) b |
24 (5–43) | — | 37% |
| Ensartinib | NCT03608007 | Prospective II | 59 | 27% (14–41) | — | — | — | 25% |
| Cabozantinib | NCT01639508 | Prospective II | — | — | — | — | — | — |
| Repotrectinib | TRIDENT | Prospective I | — | — | — | — | — | — |
| Taletrectinib | United States | Prospective I | 6 | 33% c | 4 (1–14) c | — | — | 26% |
| Japan | Prospective I | 15 | 58% d 67% b 33% c |
— | — | — | — |
a Preliminary results based on 53 patients, b Results for crizotinib-naïve patients, c Results for crizotinib-resistant patients, d Results for crizotinib-naïve and -resistant patients. Abbreviations: ORR = objective response rate; mPFS = median progression-free survival; mOS = median overall survival; CI = confidence interval; NR = not reached.