Table 1.
Completed phase III trials testing the combination of VEGF/VEGFR and PD-1/PD-L1 blocakade in solid tumors.
| Drug combination | Tumor type | Clinical Trial ID | Phase | Status | Change in PFS (months) | Change in OS (months) | Frequency of grade 3–5 adverse events | References |
|---|---|---|---|---|---|---|---|---|
| Bevacizumab + Atezolizumab | Untreated Advanced or Metastatic Hepatocellular Carcinoma (HCC) | NCT03434379 | FDA approved | Completed | 2.6 | 5.8 | 45% | Finn et al., 2020, Cheng et al., 2022 |
| Bevacizumab + Atezolizumab + Carboplatin + Paclitaxel | Untreated Metastatic Non-Squamous Non-Small Cell Lung Cancer (without EGFR and ALK mutation) | NCT02366143 | FDA approved | Completed | 1.5 | 4.5 | 58.5% | Socinski et al., 2018 |
| Bevacizumab + Atezolizumab | Untreated Advanced Renal Cell Carcinoma (RCC) | NCT02420821 | III | Completed | 2.8# (ITT) 3.5# (PD-L1+) |
0.8^ (ITT) 7.1^ (PD-L1+) |
46% | Rini et al., 2019#, Motzer et al., 2022^ |
| Bevacizumab + Pembrolizumab + platinum-based chemotherapy | Recurrent Metastatic or unresectable cervical cancer (PD-L1 combined positive score ≥ 1) | NCT03635567 | FDA approved | Completed | 2.2 | >7.9 (ITT) | 81.8% | Colombo et al., 2021 |
| Bevacizumab + Nivolumab + Carboplatin + Paclitaxel | Untreated Metastatic Non-Squamous, Non-Small Cell Lung Cancer (without EGFR and ALK mutation) | NCT03117049 | III | Active, not recruiting | 4.0 | 0.7 (interim) | 73.6% | Sugawara et al., 2021 |
| Bevacizumab + Nivolumab + Chemotherapy | Untreated Metastatic Colorectal Cancer (mCRC) | NCT03414983 | II/III | Failed to meet PFS endpoint Ɨ | 0.0 | N/A | 75% | Lenz et al., 2022 |
| Lenvatinib + Pembrolizumab | Treatment Refractory Advanced Endometrial Carcinoma | NCT03517449, NCT04865289, NCT03884101 | FDA approved | Active | 3.4 | 6.9 | 88.9% | Makker et al., 2022, Marth et al., 2021 |
| Lenvatinib + Pembrolizumab | Untreated Advanced/Metastatic Renal Cell Carcinoma | NCT02811861 | FDA approved | Active, not recruiting | 9.2 (vs. 2nd best arm) | median not reached | 82.4% | Motzer et al., 2021 |
| Cabozantinib + Nivolumab | Untreated Advanced/Metastatic Renal Cell Carcinoma | NCT03141177 | FDA approved | Active, not recruiting | 8.3 | not reached | 75.3% | Choueiri et al., 2021 |
| Axitinib + Pembrolizumab | Untreated Advanced/Metastatic Renal Cell Carcinoma | NCT02853331 | FDA approved | Active, not recruiting | 4.3 | not reached | 67% |
Rini et al., 2019
Powles et al, 2020 |
| Axitinib + Avelumab | Untreated Advanced/Metastatic Renal Cell Carcinoma | NCT02684006 | FDA approved | Active, not recruiting | 5.3 (ITT) 6.8 (PD-L1+) |
not reached | 71.2% |
Motzer et al., 2019
Choueiri et al., 2020 |
Ɨ
Although the PFS endpoint was not met, the PFS rate at 18 months were three times that of standard of care
| Pembrolizumab | PD-1 antibody |
| Nivolumab | PD-1 antibody |
| Atezolizumab | PD-L1 antibody |
| Bevacizumab | VEGFA antibody |
| Lenvatinib | Tyrosine kinase inhibitor selectively targeting VEGFR1–3, FGFR1–4, PDGFRa/b, c-Kit, and RET |
| Cabozantinib | Tyrosine kinase inhibitor selectively targeting VEGFR2, RET, MET, and AXL |