TABLE 2.
Published and ongoing clinical trials evaluating systemic therapies in high‐risk non–muscle‐invasive bladder cancer.
| Study | Study ID | Study phase, design | Patients, No. | Study cohorts | Treatment arms | End points | ||
|---|---|---|---|---|---|---|---|---|
| Published trials of systemic therapy for NMIBC | Study results/approval status | |||||||
| KEYNOTE‐057 cohort A | NCT02625961 | 2, single arm | 101 | BCG‐unresponsive CIS, with/without papillary tumors | Pembrolizumab 200 mg every 3 weeks for up to 24 months | CR at 3 months | FDA approved in January 2020 | |
| KEYNOTE‐057 cohort B | NCT02625961 | 2, single arm | 132 | BCG‐unresponsive HR NMIBC papillary tumors | Pembrolizumab 200 mg every 3 weeks for up to 24 months | HR NMIBC DFS at 12 months | The study achieved the 30% RFS at 12 months criteria set by the IBCG; however, it did not lead to FDA approval | |
| SWOG S1605 | NCT02844816 | 2, single arm | 129 | BCG‐unresponsive HR NMIBC | Atezolizumab 1200 mg every 3 weeks for up to 17 cycles | Pathological CR at 6 months for patients with CIS, and EFS at 18 months for all patients | Negative trial | |
| THOR‐2 cohort 1 | NCT04172675 | 2, randomized trial (2:1) | 73 | BCG‐treated HR NMIBC papillary tumors with FGFR alterations | Daily oral erdafitinib 6 mg for up to 2 years versus intravesical chemotherapy (mitomycin C or gemcitabine) (induction + maintenance) | RFS | Positive trial results; however, it did not lead to FDA approval | |
| Ongoing trials of systemic therapy for NMIBC | Primary completion date | Estimated completion date | ||||||
| KEYNOTE‐676 | NCT03711032 | 3, RCT | 1405 |
A: adequate BCG in HR NMIBC induction B: BCG‐naive HR NMIBC |
A1: BCG (induction + maintenance) + pembrolizumab A2: BCG (induction + maintenance) B1: BCG (induction + reduced maintenance) + pembrolizumab B2: BCG (induction + full maintenance) + pembrolizumab B3: BCG (induction + maintenance) |
A: CR at 3.5 years B: EFS at 5 years |
December 31, 2025 | October 12, 2028 |
| — | NCT04164082 | 2, single arm | 161 | BCG‐unresponsive HR NMIBC | Intravesical gemcitabine + pembrolizumab | CR for CIS at 6 months, and EFS for all patients at 18 months | March 31, 2025 | March 31, 2025 |
| ALBAN | NCT03799835 | 3, RCT | 516 | BCG‐naive HR NMIBC |
A: BCG (induction + maintenance) for 1 year B: BCG (induction + maintenance) + atezolizumab for 1 year |
RFS at 2 years | October 2024 | October 2028 |
| PREVERT | NCT03950362 | 2, single arm | 67 | BCG‐unresponsive HR NMIBC | Whole‐bladder radiotherapy (60–66 Gy) + avelumab | HR RFS at 1 year | June 15, 2023 | June 15, 2024 |
| POTOMAC | NCT03528694 | 3, RCT | 1018 | BCG‐naive HR NMIBC |
1: BCG (induction + maintenance) 2: BCG (induction + maintenance) + durvalumab 3: BCG (induction only) + durvalumab |
DFS at 4 years | October 31, 2024 | September 30, 2025 |
| ADAPT Bladder | NCT03317158 | 1/2, multiarm | 55 | BCG‐naive/relapsing/unresponsive HR NMIBC |
1: durvalumab 2: durvalumab + BCG 3: durvalumab + radiotherapy 4: durvalumab + intravesical gemcitabine/docetaxel |
Phase 1: safety Phase 2: CR |
December 31, 2024 | December 31, 2025 |
| CREST | NCT04165317 | 3, RCT | 1000 | BCG‐naive HR NMIBC |
A: sasanlimab + BCG (induction + maintenance) B: sasanlimab (induction only) C: BCG (induction + maintenance) |
EFS at 5 years | December 2, 2024 | December 2, 2026 |
Abbreviations: BCG, bacillus Calmette–Guérin; CIS, carcinoma in situ; CR, complete response; DFS, disease‐free survival; EFS, event‐free survival; FDA, Food and Drug Administration; FGFR, fibroblast growth factor receptor; HR, high‐risk; IBCG, International Bladder Cancer Group; NMIBC, non–muscle‐invasive bladder cancer; RCT, randomized controlled trial; RFS, recurrence‐free survival.