Table 1.
Results of Phase I Trials of Antiangiogenics Plus Immune Checkpoint Inhibitors for HCC
| Setting | Lenvatinib + Pembrolizumab36 | Atezolizumab + Bevacizumab42 | Nivolumab + Cabozantinib46 | Nivolumab + Cabozantinib ± Ipilimumab46 |
|---|---|---|---|---|
| First-Line | First-Line | First- or Second-Line | First- or Second-Line | |
| Efficacy results* | n=67 (%) | n=73 (%) | n=36 (%) | n=35 (%) |
| Objective response rate | 30 (44.8) | 23 (32) | 6 (17) | 9 (26) |
| Complete response | 4 (6.0) | 1 (1) | 0 | 0 |
| Partial response | 26 (38.8)** | 22 (30) | 6 | 9 |
| Disease control rate | na | 56 (77) | 29 (81) | 29 (83) |
| ≥16 weeks | 48 (66) | |||
| ≥24 weeks | 34 (47) | |||
| Median DOR (months) | 18.7 (6.9–NE) | NR (1.6–22) | 8.3 | NR |
| ≥6 months | 12/23 (52) | |||
| ≥12 months | 6/23 (26) | |||
| Median PFS (months) | na | 14.9 (0.5–23.9+) | 5.5 (3.2–10.9) | 6.8 (4.0–14.3) |
| 6-month PFS (%) | na | 71% | ||
| Median OS (months) | na | NR (0.8–24+) | 21.5 (13.1–NR) | NR (15.1–NR) |
| Safety results | n=30 (%) | n=103 (%) | n=36 (%) | n=35 (%) |
| Any AEs | 30 (100) | 95 (92) | ||
| Treatment-related AEs | 28 (93.3) | 84 (82) | ||
| Grade ≥3 | 18 (60) | 46 (45) | 17 (47) | 25 (71) |
| Serious AEs | 8 (26.7) | 36 (35) | ||
| Grade 5 | 3 (10)*** | 5 (5)*** | ||
| Dose interruptions/reductions | 18 (60)/18 (60) | na | ||
| Discontinuation | 5 (16.7) | 24 (24) | 4 (11) | 7 (20) |
Notes: *Investigator-assessed per modified RECIST in the lenvatinib plus pembrolizumab trial and per RECIST 1.1 in the bevacizumab plus atezolizumab trial. **Includes unconfirmed PRs (2 patients): ***Two grade 5 AEs in each trial were deemed treatment related.
Abbreviations: AEs, adverse events; DOR, duration of response; HCC, hepatocellular carcinoma; na, not applicable; NE, not estimable; NR, not reached; OS, overall survival; PFS, progression-free survival.