Table 2.
Combination therapies of anti-PD-1 antibodies in clinical trials.
| Agent | Target | Tumor type | Phase | Clinical indication being evaluated | Subjects | Groups in the trial and the treatment (dosing regiment and dosage level) | Clinical trials. gov number | Summary of results | Reference | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Nivolumab, ipilimumab, chemotherapy (platinum doublet) | PD-1, CTLA-4 | Lung Cancer | III | Stage IV or recurrent NSCLC patient not previously treated with chemotherapy and with a high tumor mutational burden (≥10 mutations per megabase). | 1739 | PD-L1 expression ≥1% | Nivolumab (3mg/kg every 2 wk) + ipilimumab (1mg/kg every 6 wk), n = 396 | NCT02477826 | PFS in group of nivolumab plus ipilimumab was longer than group of chemotherapy. | [58] | |
| Nivolumab (240mg every 2 wk), n = 397 | |||||||||||
| Chemotherapy (platinum doublet), n = 396 | |||||||||||
| PD-L1 expression ＜1% | Nivolumab (3 mg/kg every 2 wk) + ipilimumab (1 mg/kg every 6 wk), n = 187 | ||||||||||
| Nivolumab (360 mg every 3 wk) +chemotherapy (platinum doublet), n = 186 | |||||||||||
| Chemotherapy (platinum doublet), n = 177 | |||||||||||
| Nivolumab, ipilimumab | PD-1, CTLA-4 | Small-cell lung cancer | I/II | 18 years or older patients with an Eastern Cooperative Oncology Group performance status of 0 or 1, irrespective of PD-L1 expression and platinum sensitivity (relapse ≥90 days after chemotherapy) or resistance (relapse <90 days after or during chemotherapy). | 401 | Nivolumab (3 mg/kg every 2 wk intravenously until disease progression or unacceptable toxicity), n = 245 (TMB-evaluable, n = 133) | High TMB, n = 47 | NCT02481830 | Efficacy of nivolumab with or without ipilimumab was enhanced in patients with a high tumor mutational burden. | [59] | |
| Medium TMB, n = 44 | |||||||||||
| Low TMB, n = 42 | |||||||||||
| Nivolumab + ipilimumab (1 mg/kg plus 3 mg/kg every 3 wk intravenously, followed by nivolumab 3 mg/kg every 2 wk until disease progression or unacceptable toxicity), n = 156 (TMB-evaluable, n = 78) | High TMB, n = 26 | NCT2538666 | |||||||||
| Medium TMB, n = 25 | |||||||||||
| Low TMB, n = 27 | |||||||||||
| Nivolumab, ipilimumab | PD-1, CTLA-4 | NSCLC | I | Stage IV non-small cell lung cancer patients. | 75 | Nivolumab + ipilimumab | High TMB, n = 38 | NCT01454102 | High tumor mutation burden predicted improved objective response, durable benefit, and progression-free survival. Tumor mutation burden was independent of PD-L1 expression. | [60] | |
| Low TMB, n = 37 | |||||||||||
| Nivolumab,ipilimumab | PD-1, CTLA-4 | Melanoma | I | Metastatic melanoma patients who had not previously received treatment. | 142 | Nivolumab (1 mg/kg every 3 wk) + ipilimumab (3 mg/kg every 3 wk), followed by nivolumab (3 mg/kg every 2 wk), n = 95 Ipilimumab (3 mg/kg every 3 wk), n = 47 | NCT01927419 | The ORR and PFS of the patients with nivolumab combined with ipilimumab treatment were better than those with ipilimumab monotherapy. | [66] | ||
Abbreviations: NSCLC: non-small cell lung cancer; HCC: hepatocellular carcinoma; TMB: tumor mutational burden; ORR: objective response rate; PFS: progression-free survival; wk: weeks.