Table 2.
Ongoing clinical trials of the medical treatment for the urological cancers.
| Trial/NCT No. | Study design | Treatment | Cancer type | Patients | Primary endpoint |
|---|---|---|---|---|---|
| Renal cell cancer | |||||
| PIVOT-09/ NCT03729245 |
Phase III, randomized, open-label study | Bempegaldesleukin (NKTR-214: BEMPEG) in combination with Nivolumab compared with the investigator’s choice of a TKI therapy (either Sunitinib or Cabozantinib monotherapy) | Advanced metastatic RCC | n=623 (actual) | ORR using mRECIST 1.1 by BICR in IMDC intermediate- or poor-risk patients; ORR per mRECIST 1.1 by BICR in IMDC all-risk patients; OS in IMDC intermediate- or poor-risk patients; OS in IMDC all-risk patients |
| PDIGREE/ NCT03793166 |
Phase III, randomized, open-label study | Nivolumab and Ipilimumab followed by Nivolumab vs. Cabozantinib with Nivolumab |
Metastatic untreated RCC | n=1046 (estimated) | OS |
| COSMIC-313/ NCT03937219 |
Phase III, randomized, double-blind, controlled study | Cabozantinib with Nivolumab and Ipilimumab vs. Nivolumab and Ipilimumab |
Previously untreated advanced or metastatic RCC of intermediate or poor risk | n=840 (estimated) | Duration of PFS per RECIST 1.1 as determined by BIRC |
| CONTACT-03/ NCT04338269 |
Phase III, multicenter, randomized, open-label study | Atezolizumab + Cabozantinib vs. Cabozantinib alone |
Advanced RCC | n=500 (estimated) | PFS as assessed by IRF; OS |
| MK-6482-005/ NCT04195750 |
Phase III, open-label, randomized study | Belzutifan (MK-6482)*1
vs. Everolimus *1 Belzutifan (MK-6482): a potent and selective small molecule inhibitor of HIF-2α |
Advanced RCC | n=736 (estimated) | PFS per RECIST 1.1; OS |
| MK-6482-011/ NCT04586231 |
Phase III, open-label, randomized study | MK-6482 + Lenvatinib (MK-7902) vs. Cabozantinib [2nd-line or 3rd-line treatment] |
Advanced RCC | n=708 (estimated) | PFS per RECIST 1.1 as assessed by BICR, OS |
| MK-6482-012/ NCT04736706 |
Phase III, open-label, randomized study | Pembrolizumab (MK-3475) + Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) + Lenvatinib vs. Pembrolizumab and Lenvatinib [1st-line treatment] |
Advanced ccRCC | n=1431 (estimated) | PFS according to RECIST 1.1 as assessed by BICR; OS |
| Urothelial cancer | |||||
| CheckMate 274/ NCT02632409 (1) |
Phase III, randomized, double-blind, multi-center study | adjuvant Nivolumab vs. placebo (following surgery to remove the cancer) |
High risk invasive UC | n=709 (nivolumab n=353, placebo n=356) | DFS |
| AMBASSADOR/ NCT03244384 |
Phase III, randomized adjuvant study | MK-3475 (Pembrolizumab) vs. observation |
MIBC and locally advanced UC | n=739 (estimated) | OS; DFS |
| KEYNOTE-905/ EV-303/ NCT03924895 (2) |
Phase III, randomized study | cystectomy with perioperative Pembrolizumab and cystectomy with perioperative Enfortumab Vedotin and Pembrolizumab vs. cystectomy alone | CDDP-ineligible MIBC | n=836 (estimated) | pCR rate; EFS (in all pts, in pts whose tumors express PD-L1 CPS ≥10) |
| IMvigor010/ NCT02450331 (3) |
Phase III, open-label, multicenter, randomized study | Atezolizumab vs. observation [adjuvant therapy] |
High-risk MIUC after surgical resection | n=809 (actual) | DFS |
| KEYNOTE-866/ NCT03924856 |
Phase III, randomized, double-blind study | Perioperative Pembrolizumab (MK-3475) + NAC vs. perioperative placebo + NAC |
CDDP-eligible MIBC | n=870 (estimated) | pCR rate; EFS |
| ONO-4538-86/ CA017078/ NCT03661320 |
Phase III, randomized study | NAC alone vs. NAC + Nivolumab or Nivolumab and BMS-986205*2, followed by continued post-surgery therapy with Nivolumab or Nivolumab and BMS-986205 *2 BMS-986205 (Linrodostat): an irreversible inhibitor of IDO1 |
MIBC | n=1200 (estimated) | pCR rate; EFS |
| NIAGARA/ NCT03732677 |
Phase III, randomized, open-label, multi-center, global study | Durvalumab + GEM/CDDP for neoadjuvant treatment followed by Durvalumab alone for adjuvant treatment | Bladder cancer | n=1050 (estimated) | pCR rates at time of cystectomy; EFS per central review defined as time from randomization to event |
| DANUBE/ NCT02516241 (4) |
Phase III, randomized, open-Label, controlled, multi-center, global study | first-Line MEDI4736 (Durvalumab) monotherapy and MEDI4736 (Durvalumab) + Tremelimumab vs. SoC CTx |
Unresectable Stage IV UC | n=1126 (actual) | To assess the efficacy of Durvalumab + Tremelimumab combination therapy vs. SoC in terms of OS in FAS; To assess the efficacy of Durvalumab monotherapy vs. SoC in terms of OS in PD-L1-high analysis set |
| KEYNOTE-361/ NCT02853305 (5) |
Phase III, randomized, controlled clinical trial | Pembrolizumab with or without platinum-based combination CTx vs. CTx | Advanced or metastatic UC | n=1010 (actual) | [Pembro Combo vs. CTx]: PFS using RECIST 1.1 as assessed by BICR; OS [Pembro vs CTx]: OS in pts with PD-L1 CPS ≥10%; OS |
| CheckMate 901/ NCT03036098 |
Phase III, open-label, randomized study | Nivolumab combined with Ipilimumab or with SoC CTx vs. SoC CTx | Previously untreated unresectable or metastatic UC | n=1290 (estimated) | OS in CDDP-ineligible randomized pts; OS in PD-L1 positive (≥1%) randomized pts by IHC; PFS by BICR; OS in CDDP-eligible pts with previously untreated; unresectable or metastatic UC |
| IMvigor130/ NCT02807636 (6) |
Phase III, multicenter, randomized, placebo-controlled study | Atezolizumab as monotherapy and in combination with platinum-based CTx | Untreated locally advanced or metastatic UC | n=1200 (estimated) | PFS assessed by Investigator using RECIST 1.1 in pts treated with Atezolizumab combination therapy compared with placebo arm; OS; percentage of pts with AEs assessed using NCI-CTCAE v4.0 |
| NILE/ NCT03682068 |
Phase III, randomized, open-label, controlled, multi-center, global study | combining Durvalumab ± Tremelimumab with SoC CTx (CDDP + GEM or CBDCA + GEM doublet) followed by Durvalumab monotherapy vs. SoC alone as first-line CTx |
Metastatic bladder cancer | n=1434 (estimated) | OS |
| LEAP-011/ NCT03898180 |
Phase III, randomized, double-blind study | Pembrolizumab + Lenvatinib vs. Pembrolizumab + placebo |
Advanced/unresectable or mUC | n=694 (estimated) | PFS per RECIST 1.1 as assessed by BICR; OS |
| EV-302/ NCT04223856 |
Phase III, open-label, randomized, controlled study | Enfortumab Vedotin + Pembrolizumab vs. SoC GEM + platinum-containing CTx |
Previously untreated locally advanced or metastatic UC | n=760 (estimated) | Duration of PFS per RECIST 1.1 by BICR; Duration of OS |
| CREST/ NCT04165317 |
Phase III, multinational, randomized, open-label, three parallel-arm study | PF-06801591*3 + Bacillus Calmette-Guerin (BCG induction with or without BCG maintenance) vs. BCG (induction and maintenance) *3 PF-06801591 (Sasanlimab): an anti-PD-1 antibody |
High-risk, BCG-naïve NMIBC | n=999 (estimated) | EFS (Arm A compared to Arm C); EFS (Arm B compared to Arm C) |
| TROPiCS-04/ NCT04527991 |
Phase III, randomized, open-label study | Sacituzumab Govitecan (IMMU-132)*4
vs. treatment of physician’s choice *4 Sacituzumab Govitecan: a novel ADC combining the humanized RS7 antibody targeting Trop-2 coupled to a proprietary hydrolyzable linker |
Metastatic or locally advanced unresectable UC | n=600 (estimated) | OS |
| THOR/ NCT03390504 |
Phase III, randomized, open-label study | Erdafitinib vs. Chemotherapy (Vinflunine or Docetaxel) or Pembrolizumab | Advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death ligand 1(PD-[L]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2) | n=631 (estimated) | OS |
| Prostate cancer | |||||
| BLC3001/ NCT03748641 |
Phase III, randomized, placebo-controlled, double-blind study | Niraparib + Abiraterone acetate and PSL vs. Abiraterone acetate and PSL |
mCRPC | n=1000 (estimated) | [Cohort 1 and 3] rPFS |
| IPATential/NCT03072238 | Phase III, randomized, double-blind, placebo-controlled, multicenter trial | Ipatasertib + Abiraterone + PSL vs. placebo + Abiraterone + PSL |
mCRPC | n=1101 (actual) | Investigator-assessed rPFS per PCWG3 criteria (PTEN Loss population); Investigator-assessed rPFS per PCWG3 (ITT population) |
| ARASENS/ NCT02799602 |
Phase III, randomized, double-blind, placebo-controlled, multicenter study | Darolutamide (BAY 1841788/ODM-201) + standard ADT + Docetaxel vs. placebo + standard ADT + Docetaxel | mHSPC | n=1303 (actual) | OS |
| KEYLYNK-010/NCT03834519 | Phase III, randomized open-label study | Pembrolizumab (MK-3475) + Olaparib vs. Abiraterone acetate or Enzalutamide | mCRPC | n=780 (estimated) | OS; rPFS per PCWG-modified RECIST 1.1 as assessed by BICR |
| CAPItello-281/ NCT04493853 |
Phase III, double-blind, randomized, placebo-controlled study | Capivasertib + Abiraterone vs. placebo + Abiraterone |
de novo mHSPC by PTEN deficiency | n=1000 (estimated) | rPFS |
| TALAPRO-3/ NCT04821622 |
Phase III, randomized, double-blind study | Talazoparib + Enzalutamide vs. placebo + Enzalutamide |
DDR gene muted mCSPC | n=550 (estimated) | Radiological PFS |
ADC, antibody-drug conjugate; ADT, androgen deprivation therapy; AEs, adverse events; BCG, Bacille de Calmette et Guérin; BICR, blinded independent central review; BIRC, blinded independent radiology committee; CBDCA, carboplatin; ccRCC, clear cell renal cell carcinoma; CDDP, cisplatin; CPS, combined positive score; CRPC, castration-resistant prostate cancer; CTx, chemotherapy; DDR, DNA damage repair; DFS, disease-free survival; EFS, event-free survival; FAS, full analysis set; GEM, gemcitabine; HIF-2α, hypoxia-inducible factor 2α; IDO1, indoleamine 2,3-dioxygenase 1; IHC, immunohistochemistry; IMDC, International Metastatic RCC Database Consortium; IRF, independent review facility; ITT, intention to treat; mCRPC, metastatic CRPC; mCSPC, metastatic castration-sensitive prostate cancer; mHSPC, metastatic hormone sensitive prostate cancer; MIBC, muscle-invasive bladder cancer; MIUC, muscle-invasive urothelial cancer; mRECIST, modified RECIST; mUC, metastatic UC; NAC, neoadjuvant chemotherapy; NCI-CTCAE v4.0, National Cancer Institute-Common Technology Criteria for Adverse Events version 4.0; NMIBC, non-muscle invasive bladder cancer; ORR, objective response rate; OS, overall survival; pCR, pathological complete response; PCWG, prostate cancer working group; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1; PSL, prednisone/prednisolone; PTEN, phosphatase and tensin homolog deleted from chromosome 10; RCC, renal cell carcinoma; RECIST 1.1, response evaluation criteria in solid tumors version 1.1; rPFS, radiographic progression-free survival; SoC, standard of care; TKI, tyrosine kinase inhibitor; UC, urothelial cancer/carcinoma.