Table 3. Ongoing trials for immune checkpoint inhibitors in non-metastatic muscle invasive UC and NMIBC.
| Clinical trial number | Drug(s) investigated | Clinical setting | Study design | Phase | Primary endpoint |
|---|---|---|---|---|---|
| NCT02450331 (IMvigor010) [52] | Atezolizumab | Adjuvant in muscle invasive UC | Randomized, placebo-controlled | III | DFS |
| NCT02632409 (CheckMate-274) [53] | Nivolumab | Adjuvant in muscle invasive UC | Randomized, double-blind, placebo-controlled | III | DFS |
| NCT03244384 [54] | Pembrolizumab | Adjuvant in MIBC | Randomized, placebo-controlled | III | OS, DFS |
| NCT03387761 [55] | Nivolumab+ipilimumab | Neoadjuvant in muscle invasive UC | Single-arm trial | I | Number of patients that underwent surgical resection <12 weeks after the study started |
| NCT02845323 [56] | Nivolumab±urelumab (IgG4 monoclonal antibody to CD137) | Neoadjuvant in MIBC | Randomized to nivolumab alone or the combination | II | Immune response measured by tumor infiltrating CD8+T cell density at cystectomy |
| NCT02736266 [57] | Pembrolizumab | Neoadjuvant in MIBC | Single-arm trial | II | pCR at the time of radical cystectomy |
| NCT02365766 [58] | Pembolizumab+gemcitabine±cisplatin | Neoadjuvant in muscle invasive UC | Non-randomized | Ib/II | Phase 1b: number of patients with AEs; |
| Arm A (phase+ 1b dose finding cohort): pembrolizumab+gemcitabine/cisplatin | Phase II: rate of pathologic muscle invasive response at radical cystectomy | ||||
| Arm B (phase II cohort I): gemcitabine/cisplatin+pembrolizumab | |||||
| Arm C (phase II cohort II): gemcitabine+pembrolizumab | |||||
| NCT02662309 [59] | Atezolizumab | Neoadjuvant in MIBC | Single-arm trial | II | pCR at cystectomy, pre-and post-treatment of CD8 and/or CD3 change |
| NCT03167151 [60] | Pembrolizumab | In intermediate risk of recurrent NMIBC | Randomized | I/II | Safety, tolerability, and toxicity |
| Arm A: intravesical use | |||||
| Arm B: intravenous use | |||||
| NCT02808143 [61] | Pembrolizumab+BCG solution | In high-risk of BCG refractory NMIBC | Single-arm trial, intravesical use | I | MTD |
| NCT02625961 (KEYNOTE-057) [62] | Pembrolizumab | In high-risk of BCG unresponsive NMIBC | Single-arm trial, intravenous use | II | CR, DFS |
| NCT02844816 [63] | Atezolizumab | In high-risk of BCG unresponsive NMIBC | Single-arm trial, intravenous use | II | CR |
| NCT02792192 [64] | Atezolizumab (intravenous use)±intravesical BCG | In high-risk of BCG naïve or relapsing/unresponsive NMIBC | Non-randomized | I/II | AEs, DLTs, MTD, CR |
| Cohort 1A (BCG-unresponsive): atezolizumab | |||||
| Cohort 1B (BCG-unresponsive): atezolizumab+BCG | |||||
| Cohort 2 (BCG-relapsing): atezolizumab+BCG | |||||
| Cohort 3 (BCG-naïve): atezolizumab+BCG | |||||
| NCT02901548 [65] | Durvalumab | In BCG refractory carcinoma in the bladder | Single-arm trial, intravenous use | II | CR |
UC, urothelial carcinoma; NMIBC, non-muscle invasive bladder cancer; MIBC, muscle invasive bladder cancer; BCG, bacillus Calmette-Guérin; DFS, disease-free survival; OS, overall survival; pCR, pathologic complete response; AE, adverse event; MTD, maximum tolerated dose; CR, complete response rate; DLT, dose-limiting toxicity.