Table 4.
Ongoing phase III clinical trials of targeted therapy in urothelial carcinoma
| Experimental agent(s) | Trial ID (NCT#) | Key eligibility criteria | Experimental regimen | Comparator | Primary endpoint(s) | Estimated PCD |
|---|---|---|---|---|---|---|
| MIUC | ||||||
| Nivolumab Bempegaldesleukin |
CA045‐009 |
Cisplatin‐ineligible | Perioperative nivolumab ± Bempegaldesleukin | Observation | pCR/EFS | August 28, 2023 |
| Atezolizumab |
IMvigor‐011 |
High‐risk, ctDNA‐positive after cystectomy | Adjuvant Atezolizumab | Adjuvant Placebo | DFS | November 1, 2023 |
| Nivolumab, BMS‐986205 |
ENERGIZE |
Cisplatin‐eligible |
Neoadjuvant nivolumab + CT + BMS‐986205 or Placebo followed by adjuvant nivolumab + BMS‐986205 or placebo |
Neoadjuvant CT | pCR/EFS | November 28, 2023 |
| Infigratinib |
PROOF 302 |
Invasive UC (UTUC or BC) FGFR3‐positive |
Adjuvant Infigratinib | Adjuvant Placebo | DFS | January 31, 2024 |
| Pembrolizumab Enfortumab Vedotin |
KEYNOTE‐905 |
Cisplatin‐ineligible | Perioperative pembrolizumab +/‐Enfortumab vedotin + SR + PLND | SR + PLND | pCR/EFS | June 26, 2026 |
| Atezolizumab |
SWOG 1806 |
Localized MIBC | Atezolizumab + concurrent CRT | Concurrent CRT | BI‐EFS | June 1, 2025 |
| Pembrolizumab |
AMBASSADOR |
MIBC or locally advanced cisplatin‐ineligible |
Adjuvant pembrolizumab | Observation | DFS/OS | June 1, 2025 |
| Pembrolizumab |
KEYNOTE‐866 |
Cisplatin‐eligible | Perioperative pembrolizumab + neoadjuvant CT | Perioperative placebo + neoadjuvant CT | pCR/EFS | June 15, 2025 |
| Durvalumab |
NIAGARA |
Cisplatin‐eligible | Perioperative durvalumab + CT | Perioperative + CT | pCR/EFS | December 18, 2025 |
| Pembrolizumab |
KEYNOTE‐992 |
Localized MIBC, opting for bladder preservation | Pembrolizumab + CRT | Placebo + CRT | BI‐EFS | October 10, 2026 |
|
Cetrelimab TAR‐200 |
Not eligible for SR or opting for bladder preservation | Cetrelimab + TAR‐200 | CRT | BI‐EFS | December 30, 2026 | |
| Unresectable or metastatic UC | ||||||
| First‐line | ||||||
| Tislelizumab |
BGB‐A317‐310 |
Platinum‐eligible | Tislelizumab + CT | CT | OS | July 2022 |
| Pembrolizumab, Lenvatinib |
LEAP‐011 |
Cisplatin‐ineligible PD‐L1‐positive or platinum‐ineligible | Pembrolizumab + Lenvatinib | Pembrolizumab + Placebo | PFS/OS | December 30, 2022 |
| Durvalumab, Tremelimumab |
NILE |
Platinum‐eligible | Durvalumab + CT +/‐Tremelimumab | CT | OS | April 28, 2023 |
| Nivolumab, Ipilimumab |
CheckMate 901 |
Platinum‐eligible | Nivolumab + Ipilimumab or CT | CT | PFS/OS | October 16, 2023 |
| Enfortumab vedotin, Pembrolizumab |
EV‐302 |
Platinum‐eligible | Enfortumab vedotin + Pembrolizumab | CT | PFS/OS | November 2023 |
| Toripalimab | JS001‐038‐III‐UBC (NCT04568304) | Platinum‐eligible or ineligible PD‐L1‐positive | Toripalimab + CT | CT | PFS | November 30, 2023 |
| Second‐line and beyond | ||||||
| Rogaratinib |
FORT‐1 |
Platinum‐treated FGFR1/3‐Positive |
Rogaratinib | CT | OS (phase III stage) | October 27, 2020 |
| Erdafitinib |
THOR |
≤2 prior lines of systemic treatment PD‐(L)1i‐treated (cohort 1) and ‐naïve (cohort 2) FGFR‐positive |
Erdafitinib | CT (cohort 1) or Pembrolizumab (cohort 2) | OS | November 24, 2020 |
| Sacituzumab Govitecan |
TROPiCS‐04 |
Platinum‐treated ICI‐treated |
Sacituzumab Govitecan | CT | OS | April 2023 |
Ongoing (trials that are actively recruiting for which efficacy outcomes are not yet available) phase III trials of targeted therapy for treatment of muscle‐invasive and advanced (including locally advanced, unresectable, and metastatic) UC listed at clinicaltrials.gov on December 12, 2020, ordered by line of treatment and estimated primary completion date.
Abbreviations: BC, bladder cancer; BI‐EFS, bladder intact event‐free survival; CRT, chemoradiotherapy; CT, chemotherapy; DFS, disease‐free survival; EFS, event‐free survival; FGFR, fibroblast growth factor receptor; ICI, immune checkpoint inhibitor; ID, identifier; MIBC, muscle‐invasive bladder cancer; MIUC, muscle‐invasive urothelial carcinoma; OS, overall survival; PCD, primary completion date; pCR, pathological complete response; PFS, progression‐free survival; PLND, pelvic lymph node dissection; SR, surgical resection; UC, urothelial carcinoma; UTUC, upper urinary tract urothelial carcinoma.