Cetrelimab
Cetrelimab, an investigational programmed cell death protein receptor-1 (PD-1) inhibitor, is currently being evaluated alone and in combination with a gemcitabine-containing intravesical delivery system in clinical trials of patients with non-muscle-invasive bladder cancer.[156]ClinicalTrials.gov. A study of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone in participants with non-muscle invasive bladder cancer (NMIBC) unresponsive to intravesical Bacillus Calmette-Guérin who are ineligible for or elected not to undergo radical cystectomy (SunRISe-1). ClinicalTrials.gov Identifier: NCT04640623. Dec 2025 [internet publication].
https://clinicaltrials.gov/study/NCT04640623
[157]ClinicalTrials.gov. A study of TAR-200 in combination with cetrelimab or TAR-200 alone versus intravesical Bacillus Calmette-Guérin (BCG) in participants with BCG-naïve high-risk non-muscle invasive bladder cancer (HR-NMIBC) (SunRISe-3). ClinicalTrials.gov Identifier: NCT05714202. Dec 2025 [internet publication].
https://clinicaltrials.gov/study/NCT05714202
The gemcitabine-containing intravesical delivery system has been approved by the Food and Drug Administration (FDA) for the treatment of adults with Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ, with or without papillary tumours. Trials evaluating this device in combination with cetrelimab in different patient groups are ongoing.[156]ClinicalTrials.gov. A study of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone in participants with non-muscle invasive bladder cancer (NMIBC) unresponsive to intravesical Bacillus Calmette-Guérin who are ineligible for or elected not to undergo radical cystectomy (SunRISe-1). ClinicalTrials.gov Identifier: NCT04640623. Dec 2025 [internet publication].
https://clinicaltrials.gov/study/NCT04640623
[157]ClinicalTrials.gov. A study of TAR-200 in combination with cetrelimab or TAR-200 alone versus intravesical Bacillus Calmette-Guérin (BCG) in participants with BCG-naïve high-risk non-muscle invasive bladder cancer (HR-NMIBC) (SunRISe-3). ClinicalTrials.gov Identifier: NCT05714202. Dec 2025 [internet publication].
https://clinicaltrials.gov/study/NCT05714202
[158]ClinicalTrials.gov. A study of TAR-200 versus intravesical chemotherapy in participants with recurrent high-risk non-muscle-invasive bladder cancer (HR-NMIBC) after Bacillus Calmette-Guérin (BCG) (SunRISe-5). ClinicalTrials.gov Identifier: NCT06211764. Dec 2025 [internet publication].
https://clinicaltrials.gov/study/NCT06211764
[159]ClinicalTrials.gov. A study of TAR-200 in combination with cetrelimab and cetrelimab alone in participants with muscle-invasive urothelial carcinoma of the bladder (SunRISe-4). ClinicalTrials.gov Identifier: NCT04919512. Dec 2025 [internet publication].
https://clinicaltrials.gov/study/NCT04919512
[160]Necchi A, Guerrero-Ramos F, Crispen PL, et al. TAR-200 plus cetrelimab versus cetrelimab monotherapy as neoadjuvant therapy in patients with muscle-invasive bladder cancer who are ineligible for or decline neoadjuvant cisplatin-based chemotherapy (SunRISe-4): interim analysis of a randomised, open-label phase 2 trial. Lancet Oncol. 2025 Oct;26(10):1312-22.
http://www.ncbi.nlm.nih.gov/pubmed/40885199?tool=bestpractice.com
Cretostimogene grenadenorepvec
Cretostimogene grenadenorepvec is an investigational oncolytic adenovirus immunotherapy that selectively replicates in, and kills, tumour cells. In addition, the virus expresses granulocyte-macrophage colony-stimulating factor (GM-CSF) to induce a systemic anti-tumour immune response within the tumour cells. Cretostimogene grenadenorepvec is currently being evaluated in phase 3 studies of patients with bacille Calmette-Guérin (BCG)-unresponsive or intermediate-risk non-muscle-invasive bladder cancer.[161]ClinicalTrials.gov. Study of cretostimogene given in patients with non-muscle invasive bladder cancer ,unresponsive to Bacillus-Calmette-Guerin (BOND-003). ClinicalTrials.gov Identifier: NCT04452591. Jul 2025 [internet publication].
https://clinicaltrials.gov/study/NCT04452591
[162]ClinicalTrials.gov. A study of adjuvant cretostimogene grenadenorepvec for treatment of intermediate risk NMIBC following TURBT. ClinicalTrials.gov Identifier: NCT06111235. Sep 2025 [internet publication].
https://www.clinicaltrials.gov/study/NCT06111235
The FDA has granted fast-track designation and breakthrough therapy designation to cretostimogene grenadenorepvec for use as a potential treatment for patients with high-risk BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ.
Disitamab vedotin
An anti-human epidermal growth factor receptor-2 (HER2) antibody conjugated with monomethyl auristatin E, disitamab vedotin is being evaluated as a monotherapy in phase 2 trials of patients with HER2-positive locally advanced or metastatic urothelial carcinoma who have progressed on at least one prior line of systemic therapy.[163]Sheng X, Wang L, He Z, et al. Efficacy and safety of disitamab vedotin in patients with human epidermal growth factor receptor 2-positive locally advanced or metastatic urothelial carcinoma: a combined analysis of two phase II clinical trials. J Clin Oncol. 2024 Apr 20;42(12):1391-402.
https://ascopubs.org/doi/10.1200/JCO.22.02912
http://www.ncbi.nlm.nih.gov/pubmed/37988648?tool=bestpractice.com
Combination therapy with disitamab vedotin plus toripalimab (a PD-1 inhibitor) is being evaluated in a phase 3 study of patients with previously untreated HER2-positive locally advanced or metastatic urothelial cancer. Progression-free survival was significantly longer in patients receiving disitamab vedotin plus toripalimab compared with those randomised to gemcitabine plus cisplatin or carboplatin (13.1 months vs. 6.5 months, respectively). The safety profile of the disitamab vedotin combination was more favourable, with fewer treatment-related adverse events than chemotherapy (grade 3 or higher in 55.1% vs. 86.9%, respectively).[164]Sheng X, Zeng G, Zhang C, et al. Disitamab vedotin plus toripalimab in HER2-expressing advanced urothelial cancer. N Engl J Med. 2025 Dec 11;393(23):2324-37.
http://www.ncbi.nlm.nih.gov/pubmed/41124210?tool=bestpractice.com
Disitamab vedotin alone and in combination with toripalimab has been granted approval in China for locally advanced or metastatic urothelial carcinoma.
Microwave hyperthermia
Hyperthermia is believed to have a direct and immune-mediated cytotoxic effect on tumour cells and to improve the efficacy of mitomycin (and other chemotherapy drugs). Intravesical microwave hyperthermia and mitomycin can be used in the neoadjuvant and adjuvant setting (before or after transurethral resection, respectively). Adjuvant intravesical hyperthermic mitomycin was not superior to normothermic mitomycin (with respect to recurrence-free survival at 24 months) in prospective open label randomised trials of patients with intermediate-risk non-muscle-invasive bladder cancer.[165]Angulo JC, Álvarez-Ossorio JL, Domínguez-Escrig JL, et al. Hyperthermic mitomycin C in intermediate-risk non-muscle-invasive bladder cancer: results of the HIVEC-1 Trial. Eur Urol Oncol. 2023 Feb;6(1):58-66.
http://www.ncbi.nlm.nih.gov/pubmed/36435738?tool=bestpractice.com
[166]Tan WS, Prendergast A, Ackerman C, et al. Adjuvant intravesical chemohyperthermia versus passive chemotherapy in patients with intermediate-risk non-muscle-invasive bladder cancer (HIVEC-II): a phase 2, open-label, randomised controlled trial. Eur Urol. 2023 Jun;83(6):497-504.
https://www.sciencedirect.com/science/article/pii/S0302283822025520?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/35999119?tool=bestpractice.com