Table 3.
Clinical trials and outcomes of the combination therapies with immune checkpoint inhibitors and molecular targeted agents.
| Clinical Trial ID | Trial Name | Agents 1 | Setting 2 | Key Outcome 3 |
|---|---|---|---|---|
| Phase I/II | ||||
| NCT03299946 | CaboNivo | Cabozantinib + Nivolumab | neoadjuvant, (n = 15) |
AEs and number of patients who complete the treatment. |
| NCT03006926 | Lenvatinib + Pembrolizumab | first-line, (dose-escalation, dose-expansion), n = 30 (n = 97) |
ORR: 53.3% (34.3–71.7), DOR: 8.3 months (3.8–11.0) 4 DCR = 90.0%; 73.5–97.9, PFS: 9.7 months 7.7–NE, OS: 14.6 months 9.9–NE. |
|
| NCT03289533 | VEGF Liver 100 | Avelumab + Axitinib | AFP ≥400 ng/mL, n = 22 |
AE ORR: 13.6% (2.9–34.9) 5 DCR: 68.2 (45.1–86.1) PFS: 5.5 months (1.9–7.4) OS: 12.7 months (0.0–NE) DOR: 5.5 months (3.7–7.3) |
| NCT03418922 | Lenvatinib + Nivolumab | first-line, (n = 30) |
DLT, AEs | |
| NCT02715531 | GO30140 | Atezolizumab + Bevacizumab | n = 73 |
ORR: 27% 6
PFS: 7.5 months (0.4–23.9+) |
| NCT01658878 | CheckMate 040 | Cabozantinib + Nivolumab ± Ipilimumab | first or second-line, (dose-escalation, dose-expansion), (n = 1097, across all cohorts) | safety, tolerability, ORR |
| NCT03170960 | COSMIC-021 | Cabozantinib + Atezolizumab | first-line, (dose-escalation and dose-expansion), (n = 1732, across all cohorts) | MTD, ORR |
| NCT03347292 | Regorafenib + Pembrolizumab | first-line, (dose-escalation and dose-expansion, n = 57) | TEAE, DLT | |
| NCT03539822 | CAMILLA | Cabozantinib + Durvalumab | second-line, (n = 30) |
MTD |
| NCT03475953 | REGOMUNE | Regorafenib + Avelumab | Second-line, (n = 212) |
Recommended phase II dose, ORR |
| NCT02572687 | Ramucirumab + Durvalumab | Second-line and AFP ≥1.5x ULN, n = 28 |
DLTs ORR: 11% 7 PFS: 4.4 months (1.6–5.7) OS: 10.8 months (5.1–18.4) |
|
| NCT3463876 | RESCUE | SHR-121 (Camrelizumab) + Apatinib | n = 18 (n = 40) |
ORR: 38.9%8 DCR: 83.3% PFS: 7.2 months (2.6–NE) |
| NCT02423343 | Galunisertib (TGFβ receptor I inhibitor) + Nivolumab | second-line and AFP ≥200 ng/mL, (dose escalation and cohort expansion, n = 75) | MTD | |
| Phase III | ||||
| NCT03847428 | EMERALD-2 | Durvalumab ± Bevacizumab versus placebo | adjuvant, randomized, double-blinded, (n = 888) |
RFS |
| NCT03434379 | IMbrave150 | Atezolizumab + Bevacizumab versus sorafenib | first-line, randomized, open label, n = 501 |
OS:not reached forAtezolizumab + bevacizumabvs 13.2 months for sorafenib; HR 0.58, p = 0.006 9 PFS: 6.8 monthsforAtezolizumab + bevacizumab versus 4.3 months for sorafenib; HR 0.59, p < 0.0001 ORR: 27% |
| NCT03713593 | LEAP-002 | Lenvatinib + Pembrolizumab versus Lenvatinib | first-line, randomized, double-blinded, (n = 750) |
OS, PFS |
| NCT03755791 | COSMIC-312 | Cabozantinib + Atezolizumab versus Sorafenib versus Cabozantinib | first-line, randomized, open label, (n = 740) |
OS, PFS |
1 Bold denotes immune checkpoint inhibitors. 2 n, number of the patients analyzed in the study. The number in the parenthesis shows the number of the planned enrollment. 3 Bold denotes the primary outcome measures of the study. Duration of responses and survival are shown as median values. The numbers in the parenthesis show 95% confidential interval. 4 Ikeda et al. The American Association for Cancer Research (AACR) annual meeting 2019 (abstract #18). 5 Mudo et al. J. Clin Oncol 2019; 37 (supplement. abstract 4072). 6 Pishvaian et al. ESMO 2018 congress (# LBA26). 7 Bang et al. J Clin Oncol 2019; 37 (supplement. abstract). 8 Xu et al. J Clin Oncol 2018; 36 (supplement. abstract 4075). 9 Cheng et al. ESMO Asia2019 congress (# LBA3). DLT, dose-limiting toxicity; MTD, maximum tolerated dose; TEAEs, treatment-emergent adverse event.