Table 2.
Clinical studies on combinations of antiangiogenic agents and immunotherapies.
| Immunotherapy | Antiangiogenic therapy | Disease | Status | ClinicalTrials.gov identifier (publication) | |
|---|---|---|---|---|---|
| Vaccination Studies | |||||
| PF 06755990 (vaccine) | Sunitinib (TKI) | Prostate cancer | Phase I: | NCT02616185 | |
| Pox virus vaccine (expressing GM CSF) | Sorafenib (TKI) | HCC | Phase III: | NCT02562755 | |
| Immunostimulatory Cytokine Studies | |||||
| IFNα | Bevacizumab (anti-VEGF) | Metastatic RCC | Phase III (CALGB 90206): completed | NA (207) | |
| IFNα2A | Bevacizumab (anti-VEGF) | Metastatic RCC | Phase III (AVOREN): completed | NA (208) | |
| Cell Therapy Studies | |||||
| NK cell-based immunotherapy | Bevacizumab (anti-VEGF) | Advanced-stage solid tumors | Phase I/II: completed | NCT02857920 | |
| Autologous DC immunotherapy | Sunitinib (TKI) | Advanced-stage RCC | Phase II: completed | NCT00678119 (209) | |
| Immune-Checkpoint Blockade Studies | |||||
| Ipilimumab (anti-CTLA-4) | Bevacizumab (anti-VEGF) | Advanced-stage melanoma | Phase I: completed | NA (210) | |
| Ipilimumab (anti-CTLA-4) or Nivolumab (anti-PD-1) | Bevacizumab (anti-VEGF) | Metastatic melanoma | Phase NA: completed | NA (201) | |
| Ipilimumab (anti-CTLA-4) | Bevacizumab (anti-VEGF) | Metastatic RCC | Phase I: | NCT02210117 | |
| Ipilimumab (anti-CTLA-4) | Bevacizumab (anti-VEGF) | Melanoma | Phase II: | NCT01950390 | |
| Ipilimumab (anti-CTLA-4) | Bevacizumab (anti-VEGF) | Melanoma | Phase I: | NCT00790010 | |
| Nivolumab (anti-PD-1) | Bevacizumab (anti-VEGF) | NSCLC | Phase I: (safety and tolerability, ORR, and RFS) | NCT01454102 | |
| Nivolumab (anti-PD-1) | Sunitinib or pazopanib (TKI) | Metastatic RCC | Phase I: | NCT01472081 (211) | |
| Pembrolizumab (anti-PD-1) | Axitinib (TKI) | RCC | Phase III: | NCT02853331 | |
| Pembrolizumab (anti-PD-1) | Nintedanib (broad TKI and nTKI) | Advanced-stage solid tumors | Phase I: | NCT02856425 | |
| Pembrolizumab (anti-PD-1) | Bevacizumab (anti-VEGF) | Glioblastoma | Phase II: completed | NCT02337491 | |
| Pembrolizumab (anti-PD-1) | Ramucirumab (anti-VEGFR2) | Gastric or gastro-oesophageal adenocarcinoma, NSCLC, urothelial carcinoma, or biliary tract cancer | Phase I: completed | NCT02443324 (212) | |
| Atezolizumab (anti-PD-L1) | Bevacizumab (anti-VEGF) | Non-clear-cell RCC | Phase II: | NCT02724878 (213) | |
| Atezolizumab (anti-PD-L1) | Bevacizumab (anti-VEGF) | Metastatic cervical cancer | Phase II: | NCT02921269 | |
| Atezolizumab (anti-PD-L1) | Bevacizumab (anti-VEGF) | Multiple solid tumors | Phase I: | NCT01633970 (214) | |
| Atezolizumab (anti-PD-L1) | Bevacizumab (anti-VEGF) | Non-Small-Cell Lung Cancer | Phase III: | NCT02366143 (215, 216) | |
| Atezolizumab (anti-PD-L1) | Vanucizumab (bi‑specific mAb targeting VEGF and ANG2) | Advanced-stage solid tumors | Phase I: completed (MTD, AEs, and ORR) | NCT01688206 | |
| Avelumab (anti-PD-L1) | Axitinib (TKI) | Advanced-stage RCC | Phase I: | NCT02493751 (217) | |
| Avelumab (anti-PD-L1) | Axitinib (TKI) | Advanced-stage RCC | Phase III: | NCT02684006 (218, 219) | |
| Selicrelumab (RO7009789-agonistic anti‑CD40 mAb) | Vanucizumab (bi‑specific mAb targeting VEGF and ANG2) | Metastatic solid tumors | Phase I: completed (safety, pharmacokinetics and pharmacodynamics, and therapeutic activity) | NCT02665416 | |
| Durvalumab (anti-PD-L1) | Ramucirumab (anti-VEGFR2) | Gastric or gastro-oesophageal adenocarcinoma, NSCLC or HCC | Phase I: | NCT02572687 | |
| SHR‑1210 (anti‑PD‑1 mAb) | Apatinib (TKI, VEGFR2) | Gastric cancer and HCC | Phase I/II: (tumor control rate, disease control rate, OS, and AEs) | NCT02942329 (220) | |