FIGURE 2.

Immunotherapy Combination Clinical Trials in various stages of development utilizing immune therapies in combination with other immune therapies, chemotherapy, tyrosine kinase inhibitors, and other agents. Trials are further subdivided by disease state, into nonmuscle-invasive bladder cancer, muscle-invasive bladder cancer, metastatic first line, and metastatic second line. ¹Objective response rate 38% for Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg (n = 26; complete response 3.8%). Objective response rate 26% for Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (n = 104; complete response 2.9%). SITC 2016. ²Immune checkpoint inhibitor of the adenosine A2A receptor. ³Oral inhibitor of indoleamine 2,3-dioxygenase 1. ⁴Oncolytic group B adenovirus vaccine. ⁵mAb against CD137 receptor. ⁶mAb against B7-H3. ⁷Personalized cancer vaccine. ⁸mAb against CD27. ⁹Antibody-cytokine conjugate consisting of two heterodimers of IL-12, fused to a human mAb that has affinity for both single-stranded and double-stranded DNA. ¹⁰Poxvirus-based vector vaccine that induces tumor-specific immune response in T cells. ¹¹IL-2 genetically fused to a humanized soluble T-cell receptor directed against the p53-derived peptides expressed on tumor cells. ¹²Objective response rate in five chemo-naïve patients 100% (two complete responses and three partial responses) and in five previously treated patients 60% (one complete response and two partial responses), for an overall objective response rate of 80% (three complete responses, five partial responses, 1 stable disease, and 1 progressive disease). Fishman et al.[22]. ¹³Objective response rate 64% (partial response 50%; complete response 14%); Galsky et al.[23]. ¹⁴Autologous dendritic cell-based immunotherapy. ¹⁵mAb against FGFR3. ¹⁶Second-generation Bruton's tyrosine kinase inhibitor. ¹⁷Tyrosine kinase inhibitor of VEGFR2. ¹⁸Tyrosine kinase inhibitor of KIT, CSF1R, and FLT3. ¹⁹Formulation of coxsackievirus type A21. ²⁰Recombinant protein inhibitor of tumor growth and angiogenesis, complete response in one of three patients in higher dose cohort. https://www.viralytics.com/wp-content/uploads/2014/05/160315-EAU-CANON.pdf. ²¹mAb against VEGFR2. ²²Humanized IgG4 (kappa) isotype mAb against CEACAM1. ²³TLR3 agonist. BCG, Bacillus Calmette–Guérin; MIBC, muscle-invasive bladder cancer; NMIBC, nonmuscle-invasive bladder cancer; UC, urothelial carcinoma.