Profile of pembrolizumab in the treatment of patients with unresectable or metastatic urothelial carcinoma

Figures & data

Figure 1 Mechanisms of action of ICIs.

Abbreviations: APC, antigen-presenting cell; TCR, T cell receptor; PD-1, programmed cell death 1; PD-L, programmed death ligand; CTLA-4, cytotoxic T lymphocyte-associated protein 4.

Table 1 Immune checkpoint inhibitors (ICIs) for patients with unresectable or metastatic urothelial carcinoma (UC)

	Target	Type	FDA approval	Trial phase based on approval	Assay for PD-L1 expression
Pembrolizumab	PD-1	IgG4	Post-platinum-based chemotherapy*	Phase III	Dako PD-L1 IHC 22C3 pharmDx assay
			First-line, cisplatin-ineligible	Phase II
Nivolumab	PD-1	IgG4	Post-platinum-based chemotherapy	Phase II	Dako PD-L1 IHC 28–8 pharmDx assay
Atezolizmab	PD-L1	IgG1	Post-platinum-based chemotherapy	Phase II	VENTANA PD-L1 (SP142) assay
			First-line, cisplatin-ineligible	Phase II
Durvalumab	PD-L1	IgG1	Post-platinum-based chemotherapy	Phase I/II	VENTANA PD-L1 (SP263) assay
Avelumab	PD-L1	IgG1	Post-platinum-based chemotherapy	Phase Ib	Dako PD-L1 IHC73-10 pharmDx assay

Note: *Regular approval.

Table 2 Ongonig Phase III trials of pembrolizumab in patients with unresectable or metastatic urothelial carcinoma

Disease setting	Study title		ClinicalTrials.gov Identifier	Intervension	Study design* (Estimated/actual primary completion date)	Primary endpoint
1st-line	A Phase III Randomized, Controlled Clinical Trial of Pembrolizumab With or Without Platinum-Based Combination Chemotherapy Versus Chemotherapy in Subjects With Advanced or Metastatic Urothelial Carcinoma	MK-3475–361 KEYNOTE-361	NCT02853305	Pembrolizumab	N=990 Active not recruiting (June, 2019)	PFS/OS
				vs pembrolizumab+chemotherapy
				vs chemotherapy
1st-line, cisplatin-ineligible	A Phase III Randomized, Double-Blind Trial of Pembrolizumab (MK-3475) in Combination With Epacadostat (INCB024360) or Placebo in Participants With Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)	KEYNOTE-672 ECHO-307	NCT03361865	Pembrolizumab + epacadostat	N=94 Active Enrollment was halted (August, 2018)	ORR
				vs pembrolizumab + placebo
2nd-line	A Phase III Randomized, Double-Blind Clinical Study of Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo as a Treatment for Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients Who Have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease (KEYNOTE-698/ECHO-303)	KEYNOTE-698 ECHO-303	NCT03374488	Pembrolizumab + epacadostat	N=84 Active Enrollment was halted (July, 2018)	ORR
				vs pembrolizumab + placebo
2nd-line, with FGFR aberrations	A Phase III Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations	BLC3001	NCT03390504	Erdafitinib	N=631 Active Recruiting (November, 2020)	OS
				vs vinflunine or docetaxel (cohort 1)
				vs pembrolizumab (cohort 2)

Note: *Recruitment status in March 2019.