Table 2. Approval status and clinical development of immune checkpoint inhibitors.

Agent	Characteristics	Clinical studies leading to drug approval and current status of clinical development relative to histological tumor type		FDA Approval
Anti-PD-1 agents
Nivolumab	Fully human anti-PD-1 IgG4k mAb	Melanoma	· In a phase III trial, ORR was 31.7% (95% CI 23.5-40.8) in the nivolumab group vs 10.6% (95% CI 3.5-23.1) in the ICC group [229]. In a phase III trial, 1 year-OS was 72.9% (95% CI 65.5-78.9) in the nivolumab group vs 42.1% (95% CI 33.0-50.9) in the dacarbazine group (HR for death, 0.42; 99.79% CI 0.25-0.73; p < 0.001) [230]. In a phase III trial, median PFS was 11.5 months (95% CI 8.9-16.7) with nivolumab+ipilimumab, vs 2.9 months (95% CI 2.8-3.4) with ipilimumab (HR for death or disease progression, 0.42; 99.5% CI 0.31-0.57; p < 0.001), and 6.9 months (95% CI 4.3-9.5) with nivolumab (HR for the comparison with ipilimumab, 0.57; 99.5% CI 0.43-0.76; p < 0.001) [231].	∙ In patients with unresectable or metastatic melanoma who no longer respond to other drugs (2014). ∙ In combination with ipilimumab for the treatment of patients with BRAF V600 wild-type and BRAF V600 mutation-positive unresectable or metastatic melanoma (2015, 2016).
		NSCLC	In a phase III trial (on squamous-NSCLC patients), median OS was 9.2 months (95% CI 7.3-13.3) with nivolumab vs 6.0 months (95% CI 5.1-7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (HR 0.59; 95% CI 0.44-0.79; p < 0.001). At 1 year, the OS rate was 42% (95% CI 34-50) with nivolumab vs 24% (95% CI 17-31) with docetaxel [232]. In a phase III trial (on nonsquamous-NSCLC patients), median OS was 12.2 months (95% CI 9.7-15.0) in the nivolumab group and 9.4 months (95% CI 8.1-10.7) in the docetaxel group (HR for death 0.73; 96% CI 0.59-0.89; p = 0.002). The 18-months OS rate was 39% (95% CI 34-45) with nivolumab vs 23% (95% CI 19-28) with docetaxel [233].	∙ In patients with metastatic NSCLC with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab (2015).
		RCC	In a phase III trial, median OS was 25.0 months (95% CI 21.8-not estimable) with nivolumab and 19.6 months (95% CI 17.6-23.1) with everolimus. HR for death with nivolumab vs everolimus was 0.73 (98.5% CI 0.57-0.93; p = 0.002) [234].	∙ In patients with metastatic RCC who have progressed on an anti-angiogenic agent (2015).