Table 2.
Clinical trials on the association of antiangiogenic with immunotherapy or anti-BRAF/anti-MEK targeted therapy in advanced melanoma.
| Reference | Phase | Clinical setting | Line of treatment in metastatic setting | Arm 1 | Arm 2 | Primary endpoints | Secondary endpoints | Further details |
|---|---|---|---|---|---|---|---|---|
| Hodi et al. (78) | I | Stage III unresectable or stage IV melanoma. No brain metastases | 1st or 2nd line (46 pts) |
Ipilimumab + Bevacizumab | None | ORR 8 PR, 22 SD | DCR 67% OS 25 m |
|
| NCT01950390 | II randomized | Stage III unresectable or IV cutaneous melanoma. No brain metastases |
1st or 2nd line (168 pts) |
Ipilimumab | Ipilimumab + Bevacizumab |
OS | PFS ORR |
Active, not recruiting. Results pending |
| Taylor et al. (79) | IB/II | Advanced solid tumors including melanoma | 2nd or 3rd line (21 pts with melanoma) |
Pembrolizumab + Lenvatinib | None | Safety | ORR at week 24 48% in melanoma (1 CR and 9 PR) | |
| Arance et al. (80) | II | Stage III unresectable or IV cutaneous melanoma. | 2nd or further line (103 pts) | Pembrolizumab + Lenvatinib | None | ORR 21.4% | PFS 4.2 m OS 13.9 m |
|
| NCT03820986 | III randomized |
Stage III unresectable or IV cutaneous melanoma. No active brain metastases |
1st or 2nd line (660 pts) |
Pembrolizumab + Lenvatinib | Pembrolizumab + Placebo | PRS OS |
ORR DOR Toxicity |
Active, recruiting |
| NCT01495988 | II | Stage IIIC unresectable or stage IV melanoma. BRAF V600E/V600K positive. No active brain metastases |
1st or further line (10 pts enrolled, vs initially designed 180 pts) | Vemurafenib + Cobimetinib + Bevacizumab (arm 2) |
Vemurafenib + Cobimetinib (arm 1) Vemurafenib (arm 3) Vemurafenib + Bevacizumab (arm 4) |
PFS | OS RR Toxicity (2 pts in arm 2. 1 of them, multi-organ failure) |
Slow accrural, toxicity, change in priorities |
| NCT04356729 | II | Stage III unresectable or IV cutaneous melanoma PDL1 negative. No active brain metastases |
Any line (no prior immunotherapy) | Atezolizumab + Bevacizumab (30 estimated pts) |
None | ORR | OS TTP DOR Safety Change in TILs |
Not yet recruiting |
| NCT03175432 | II | Stage IV melanoma with brain metastases. BRAF wt | Progression after anti-PD1 | Atezolizumab + Bevacizumab + Cobimetinib |
None | Intracranial ORR Safety |
ORR DOR Neurocognitive function |
Recruiting. Estimated 60 pts |
| NCT02681549 | II | Stage IV melanoma or NSCLC with brain metastases | 2nd or further line | Pembrolizumab + Bevacizumab | None | Intracranial ORR | Need for steroids ORR PFS Safety Biomarkers |
Recruiting. Estimated 53 pts |
| NCT03239145 | I | Advanced solid tumors. No active brain metastases |
2nd or further line | Pembrolizumab + Trebananib | None | Maximum dose | ORR PFS OS |
Recruiting. Estimated 60 pts |