Table 2A.
The clinical trials of the combination of PD-1/PD-L1 blockade with Other ICB in cancer therapy
| Targets | PD-1/PD-L1 blockade | Other ICB | Clinicaltrial no. | Phase | Tumor types | Findings | References |
|---|---|---|---|---|---|---|---|
| PD-1×CTLA-4 | Nivolumab | Ipilimumab | NCT03033576 | II | Refractory metastatic melanoma | The combination of nivolumab and ipilimumab resulted in a statistically significant improvement in PFS over ipilimumab (hazard ratio, 0.63, p = 0.04). ORR were 28% and 9%, respectively (p = 0.05). | 194 |
| PD-1×CTLA-4 | Nivolumab | Ipilimumab | NCT02716272 | II | Relapsed malignant pleural mesothelioma | In the nivolumab group, 24 (44%) of 54 patients achieved 12-week disease control, compared to 27 (50%) of 54 in the combination group. In the intention-to-treat population, 25 (40%) of 63 in the nivolumab group and 32 (52%) of 62 in the combination group achieved 12-week disease control. | 195 |
| PD-1×CTLA-4 | Nivolumab | Ipilimumab | NCT01844505 | III | Melanoma | Median PFS was 11.5 months for combined treatment (2.9 months for ipilimumab alone, 6.9 months for nivolumab alone). In PD-L1-positive patients, median PFS was 14.0 months for both combination and nivolumab alone groups. In PD-L1-negative patients, combination PFS was 11.2 months vs 5.3 months with nivolumab alone. | 196 |
| PD-L1×CTLA-4 | Durvalumab | Tremelimumab | NCT02592551 | II | Malignant pleural mesothelioma | Patients receiving combination blockades had longer median overall survival compared with those receiving monotherapy. Tumor PR occurred in 6 of 17 patients receiving ICB and thoracotomy (35.3%), among which major PR (>90% tumor regression) occurred in 2 (11.8%). | 197 |
| PD-L1×CTLA-4 | Durvalumab | Tremelimumab | NCT02319044 | II | Recurrent or metastatic HNSCC | Objective response rate was 7.8% in the combination arm (n = 129), 9.2% for durvalumab monotherapy (n = 65), and 1.6% for tremelimumab monotherapy (n = 63); median overall survival for all patients treated was 7.6, 6.0, and 5.5 months, respectively. | 198 |
| PD-1×CTLA-4 | Cadonilimab | NCT04220307 | II | Recurrent or metastatic nasopharyngeal carcinoma | ORR was 26.1 %. The ORR were 44.4 % and 14.3 % in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % of patients with EBV-DNA level <4000 IU/ml and 15.4 % of those with ≥4000 IU/ml. | 199 | |
ICB: immune checkpoint blockades; ORR: objective response rate; DCR: disease control rate; PFS: progression-free survival; PR: partial response; HNSCC: head and neck squamous cell carcinoma.