Table 2. . US FDA-approved second-line immune checkpoint inhibitors for metastatic bladder cancer.

Trial	Phase	Mechanism of action	Dosage	Primary end points	Secondary end points	Results of primary end point
CheckMate-275	Single-arm Phase II	PD-1 inh	Nivolumab 3 mg/kg IV every 2 weeks (n = 265)	ORR	OS	Confirmed objective response = 28.4%, 95% CI: 18.9–39.5
KEYNOTE-045	III	PD-1 inh vs. chemotherapy	Pembrolizumab 200 mg IV every 3 weeks	OS + PFS	ORR	Pembrolizumab OS = 10.3 mos vs chemotherapy = 7.4 mos; p = 0.002
IMvigor210	Single-arm, two-cohort, Phase II trial	PD-L1 inh	Atezolizumab 1200 mg IV every 3 weeks	Independent review and investigator-assessed ORR	AEs and SAEs	ORR for IC2/3: 27%; IC1/2/3: 18%; all patients (15%)
JAVELIN	Ib	PD-L1 inh	Avelumab 10 mg/kg IV every 2 weeks	Safety and tolerability	ORR, PFS, OS	ORR independent central review = 18.2%
Study 1108	I/II	PD-L1 inh	Durvalumab 10 mg/kg every 2 weeks	Safety	Confirmed ORR	AEs: fatigue (13.1%), diarrhea (9.8%) and decreased appetite (8.2%); ORR was 31.0% (95% CI: 17.6–47.1)

AE: Adverse event; AE: Adverse effect; DLT: Dose-limiting toxicity; Inh: Inhibitor; IV: Intravenously; MTD: Maximum tolerated dose; ORR: Objective response rate; OS: Overall survival; PD-L1: PD-1 ligand; PFS: Progression-free survival; q: Every; RD: Recommended dose; SAE: Serious adverse event.