Bladder Cancer Trials

This is a phase 3, open label, single arm study of TOOKAD (padeliporfin, a type of targeted therapy) in the treatment of Upper Tract Urothelial Carcinoma (UTUC). The ENLIGHTED study will recruit patients with low-grade upper tract urothelial carcinoma in either the kidney or the ureter. The patients will be treated with TOOKAD VTP in two phases: an Induction Treatment Phase and a Maintenance Treatment Phase and will be followed up for additional 12 months in the long term (non-intervention) follow up phase. The study has 1 treatment arm: Patients entered in the study will undergo an induction treatment phase consisting of 1-3 TOOKAD VTP treatments provided 4 weeks (28 +/-3 days) apart. Patients achieving a complete response (CR, no further evidence of your cancer) after the induction treatment phase will be allowed into the maintenance treatment phase. Repeated maintenance VTP treatments during this period will be provided for patients who show evidence of tumor recurrence that is deemed treatable. During treatment, an optical light fiber will be placed at a determined target area, through a ureteroscope. Intravenous (IV) administration of TOOKAD at the dose of 3.66 mg/kg will be infused over 10 minutes. Each target area will be illuminated for 10 minutes.

This phase II trial studies how well olaparib (a type of targeted therapy/PARP inhibitor) works in treating patients with urothelial cancer (with DNA-repair defects) that has spread to other places in the body (metastatic) and usually cannot be cured or controlled with treatment. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The study has 1 arm: Treatment (olaparib) Patients receive olaparib by mouth (orally) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity/side effects.

This study will test an experimental drug (enfortumab vedotin, a type of targeted therapy) alone and with different combinations of anticancer therapies. Pembrolizumab (Keytruda, a type of immunotherapy) is used to treat patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra. Some parts of the study will look at locally-advanced and metastatic urothelial cancer, which means the cancer has spread to nearby tissues or to other areas of the body. Other parts of the study will look at muscle-invasive bladder cancer (MIBC), which is cancer at an earlier stage that has spread into the muscle wall of the bladder. This study will look at the side effects of enfortumab vedotin alone and with other anticancer therapies. A side effect is a response to a drug that is not part of the treatment effect. This study will also test if the cancer shrinks with the different treatment combinations. Treatment – each cycle is 21 days. ALL treatment medications are given intravenously (IV) in clinic. Treatment arm, type of treatment (or combination) and dosages will be provided in detail by your treatment provider. Monotherapy: Enfortumab vedotin (EV) on days 1 and 8 every 21 days. EV + Pembrolizumab: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days. EV + Cisplatin (a type of chemotherapy): Enfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days. EV + Carboplatin (a type of chemotherapy): Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days. EV + Gemcitabine (a type of chemotherapy): Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days. EV + chemotherapy + Pembrolizumab Enfortumab vedotin on days 1 and 8 plus cisplatin or carboplatin on day 1 plus pembrolizumab on day 1 every 21 days.

This is an open-label, multicenter, Phase 1, ascending dose escalation study of PSB205 (a type of immunotherapy) in subjects with advanced solid tumors, including bladder and kidney cancer. This study purpose is to describe the safety and tolerability, to assess Pharmacokinetics (PK, how the drug moves through your body) and immunogenicity (the effect on the immune system), and to preliminarily assess the anti-tumor activity of PSB205 in subjects with solid tumors. All subjects will receive study drug. Specific dosing will be provided by your treating physician. PSB205 will be administered on day 1 of every 21-day cycle (3 weeks) by intravenous (IV) infusion.

A global, randomized phase III study to evaluate perioperative (before and after surgery) pembrolizumab (Keytruda, a type of immunotherapy) with surgery (radical cystectomy + pelvic lymph node dissection (RC+PLND) versus RC+PLND alone) in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC). This study has 2 arms: Arm A: Pembrolizumab + Surgery Participants receive 3 preoperative cycles of pembrolizumab, followed by standard of care surgery, followed by up to 14 cycles of postoperative pembrolizumab. Pembrolizumab 200 mg by given by intravenous (IV) infusion on Day 1 of each 21-day cycle. Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines. Arm B: Surgery alone Participants receive standard of care surgery alone.

This is a single-arm phase 2 window of opportunity study to assess the antineoplastic activity of pemigatinib (an orally administered inhibitor of fibroblast growth factor receptors 1, 2, and 3; a type of targeted therapy) in non-muscle invasive bladder cancer (NMIBC) patients with recurrent tumors and a prior history of low- or intermediate-risk NMIBC tumors. Enrolled patients will receive pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT). The study will assess both safety and effectiveness of pemigatinib. This study has 1 arm: Treatment: Pemigatinib Participants will take Pemigatinib is taken orally once daily on days 1 through 28 of each cycle. Patients will receive pemigatinib for 4 to 6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).

Tumors in the genitourinary tracts can occur in the kidney, bladder, prostate, and testicles and can have common and rare histologies. Some cancers that occur along the genitourinary (GU) tract are rare. Some GU tumors are so rare that they are not included in treatment studies or tissue banks. This makes it hard for researchers to determine standards of care. Researchers want to learn more about common and rare GU tumors. The objective of this study is to learn more about urinary tract cancers. Rare histological variants of the GU tract include bladder/urachal adenocarcinoma, squamous cell carcinoma, and small cell carcinoma; variants of urothelial carcinoma including plasmacytoid, sarcomatoid; renal tumors including sarcomatoid renal cell carcinoma and renal medullary carcinoma; penile cancers; micropapillary, giant cell, lipid rich, clear cell and nested variants, large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns; small cell neuroendocrine carcinoma of the prostate, testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC. Some GU tumors occur so infrequently that they are not systematically captured by currently available registries, treatment protocols or tissue banks. The rarity of these tumors limits the sufficient numbers of patients needed in larger randomized clinical studies to characterize standard treatments or disease course. Systematic and longitudinal collection and annotation of clinical history, tissue samples, imaging studies, participant reported outcomes, and other pertinent information in participants with these rare tumors will yield future knowledge and help with the development of subsequent prospective studies to optimize diagnosis and treatment paradigms for less common GU tumors. There is no treatment given as part of this study. This will be a long-term study to comprehensively study participants with rare GU tumors. Medical history will be collected, and participants followed throughout the course of their illnesses, with particular attention to patterns of disease presentation, recurrence and progression, response to therapies, duration of responses and participant reported outcomes. Tissue samples and blood will be obtained from participants during this study. A broad spectrum of scientific experiments, including genomics and immune monitoring will be performed.

Bladder cancer is the most common urinary tract cancer and the 5th most common cancer in the US (1). Yet bladder cancer research is underfunded relative to other common cancers. As a result, bladder cancer care is prone to evidence gaps that produce decision uncertainty for both patients and clinicians. The Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) for Bladder Cancer Study has the potential to fill these critical evidence gaps, change care pathways for the management of NMIBC (non-muscle-invasive bladder cancer), and provide for personalized, patient-centered care. The purpose of CISTO is to conduct a large prospective study that directly compares the impact of medical management versus bladder removal in recurrent high-grade NMIBC patients with BCG (Bacillus Calmette-Guerin) failure on clinical outcomes and patient and caregiver experience using standardized patient-reported outcomes (PROs). There is no treatment given as part of this protocol. Treatment will be determined by your treating physician.

This phase II trial studies how well cabozantinib (Cabometyx, a type of targeted therapy) works in combination with nivolumab (Opdivo, a type of immunotherapy) and ipilimumab (Yervoy, a type of immunotherapy) in treating patients with rare genitourinary (GU) tumors that have spread to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone. All participants will receive treatment: Treatment (cabozantinib, nivolumab, ipilimumab) Patients will take cabozantinib orally (PO) QD on days 1-21 of cycles 1-4, and on days 1-28 of subsequent cycles. Patients also receive nivolumab intravenously (IV) over 30 minutes on day 1 and ipilimumab IV over 90 minutes on day 1 of cycles 1-4. Patients then receive nivolumab IV over 30 minutes on day 1 of subsequent cycles. Treatment repeats every 21 days for cycles 1-4 and every 28 days for subsequent cycles for 2 years.

This study is designed to assess the antitumor effect and safety of pembrolizumab (Keytruda, a type of immunotherapy) in combination with chemoradiotherapy (CRT, chemotherapy + radiation therapy) versus CRT alone in participants with muscle-invasive bladder cancer (MIBC). The primary hypothesis (or thought about the study) is that pembrolizumab + chemoradiotherapy is superior to placebo + chemoradiotherapy for intact bladder progression free survival. This study has 2 arms: Arm A: Pembrolizumab + Chemotherapy + Radiotherapy Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by your provider. Pembrolizumab at 400 mg given intravenously (IV) once every 6 weeks. Details of chemotherapy and radiotherapy regimens will be discussed with your provider. Arm B: Placebo + Chemotherapy + Radiotherapy Participants receive placebo plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator. Placebo given intravenously (IV) once every 6 weeks. Details of chemotherapy and radiotherapy regimens will be discussed with your provider.

This is a Phase III, global, multicenter, open-label randomized controlled trial in patients with metastatic or locally advanced unresectable urothelial cancer (UC) who have progressed after prior therapy with platinum-based regimen (chemotherapy) and anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy (immunotherapy). Subjects will be randomized to either sacituzumab govitecan (a combination of chemotherapy and immunotherapy) arm or Treatment of Physician's Choice arm. This study has 2 treatment arms: Arm A: sacituzumab govitecan Subjects randomized to this treatment arm will receive 10 mg/kg of sacituzumab govitecan intravenously (IV) on Day 1 and Day 8 of each 21-day cycle. Arm B: Treatment of Physician's Choice Those randomized to the Treatment of Physician's Choice arm will have the choice of receiving paclitaxel (a type of chemotherapy), docetaxel (a type of chemotherapy), and vinflunine (a type of chemotherapy) administered intravenously (IV) at standard of care doses of 175, 75 and 320 mg/m2 respectively, on Day 1 of each 21-day cycle.

This is an open label, Phase I-II, first in human (FIH) study for SKB264 (a type of targeted therapy) as monotherapy in patients who have locally advanced unresectable or metastatic solid tumor that is refractory to all standard therapies, including bladder cancer. TROP2 (trophoblast antigen 2) assessments will not be performed prior to enrollment but it will be assessed retrospectively. Confirmation of TROP2 (trophoblast antigen 2) expression by immunohistology or other means is not required, but the Sponsor will request fresh tumor biopsy or tissue specimens from archived materials for determination of TROP2 (trophoblast antigen 2) expression retrospectively. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy whose tumor is refractory to standard therapies. Patients will receive study drug as a single intravenous (IV). Specific dose level and dosing schedule will be provided by your treating physician. Cycles will continue until disease progression or unacceptable toxicity.

Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug M9241 triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation. This study has 3 treatment arms: Arm A: Treatment with M7824 and deescalating (decreasing) doses of M9241, if appropriate Drug: M7824 1200 mg administered intravenously (IV) in clinic every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously (SC or SQ) every 4 weeks while on M7824 and with or without SBRT Arm B: Treatment with M7824 and deescalating doses of M9241 (if appropriate) with sequential SBRT Drug: M7824 1200 mg administered IV every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT Radiation: Stereotactic body radiation therapy (SBRT) a fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241 Arm C: Treatment with M7824 and deescalating doses of M9241 (if appropriate) with concurrent SBRT Drug: M7824 1200 mg administered IV every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT Radiation: Stereotactic body radiation therapy (SBRT) a fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241

This is a registry study to gather more information on the current use of Blue Light Cystoscopy with Cysview (BLCC) in urologists' practices. The Blue Light Cystoscopy with Cysview Registry is a web-based program supported by Global Vision Technologies. Data will be captured longitudinally over five (5) years on patients from each enrolled site. Each center will enter their respective site's patient data electronically. This study does NOT offer any treatment.

This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab (Tecentriq, a type of immunotherapy) in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab. This study has 2 treatment arms: Arm A: Radiation Therapy (RT) + Chemotherapy Patients undergo RT Monday-Friday for up to 7 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine intravenously (IV) twice weekly for 6 weeks, OR cisplatin IV weekly for 6 weeks concurrent with RT, OR fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy PLUS mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Arm B: RT + chemotherapy + atezolizumab Patients undergo RT Monday-Friday for up to 7 weeks and receive chemotherapy based on physician's choice as in Arm A. Patients also receive atezolizumab IV over 60 minutes on day 1 of chemotherapy. Treatment repeats every 21 days for a total of 6 months (9 doses total) in the absence of disease progression or unacceptable toxicity.

This study evaluates the post-cystectomy (surgical removal of the bladder) CD8+ tumor response of patients receiving nivolumab (an immunotherapy) plus urelumab (an immunotherapy) versus nivolumab alone. It is hypothesized that giving these drugs together will improve patients’ response rates (increase anti-tumor activity) more than either drug given alone. Half the patients will receive nivolumab plus urelumab, while the other half will receive nivolumab alone. The study participants will have muscle invasive urothelial carcinoma of the bladder (MIBC) that is not suitable for cisplatin-based chemotherapy, but be fit to undergo surgical resection of their cancer by cystectomy. Patients with resectable clinical node positive disease within the true pelvis (N1) are eligible.

Nivolumab 240 mg will be administered by one-hour intravenous infusion on Day 1 and Day 15 for two cycles. Urelumab 8mg will be administered by one-hour intravenous infusion on Day 1 for two cycles.

The study is investigating the ability of UroGen's MitoGel procedure to treat urothelial carcinoma tumors from the upper urinary tract. If this treatment will prove to be effective this will lead to the development of a new treatment approach for patients suffering from Low Grade Upper Urinary Urothelial Carcinoma (UTUC).

MitoGel will be instilled directly into the bladder using a catheter. Treatment with MitoGel is given once weekly for a total of 6 treatments. Patients who will demonstrate complete response (meaning your cancer is no longer visible) will be treated with MitoGel once monthly as a maintenance therapy for a total of 11 treatments.

The purpose of this study is to determine if TAR-200 (GemRIS), an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) between diagnosis and radical cystectomy (RC). TAR-200 is a passive, non-resorbable (meaning it only acts locally in the bladder and will not be absorbed into the body) gemcitabine (Gemzar, a type of chemotherapy) releasing intravesical (in the bladder) drug delivery system, regulated as a drug, whose primary mode of action is the controlled release of gemcitabine into the bladder over a 7-day period.

There are two arms in this study:

Arm A: Patients who have residual disease after surgical removal of the bladder tumor (TURBT)

TAR-200 is placed into the bladder through a catheter on Study Day 0 and is removed on Study Day 7. TAR-200 releases gemcitabine gradually during the 7 day indwelling time. A second TAR-200 is placed in the bladder on Study Day 21 and is removed on Study Day 28, which is the day of the Radical Cystectomy (RC, surgery that removes the entire bladder).

Arm B: Patients who do NOT have residual disease after surgical removal of the bladder tumor (TURBT)

TAR-200 is placed into the bladder through a catheter on Study Day 0 and is removed on Study Day 7. TAR-200 releases gemcitabine gradually during the 7 day indwelling time. A second TAR-200 is placed in the bladder on Study Day 21 and is removed on Study Day 28, which is the day of the Radical Cystectomy (RC).

Non-muscle-invasive bladder cancer is in the early stages, but it usually comes back after treatment. The drugs Vicinium (a type of targeted therapy) and Durvalumab (a type of immunotherapy) may help the immune system find and destroy cancer cells. The objective of this study is to test if the drugs Durvalumab and Vicinium together are safe and effective to treat people with bladder cancer that has not spread to the muscle in the bladder. All patients will receive: Durvalab 1500 mg administered intravenously (IV) once every 4 weeks for 12 months provided that the patient is tolerating therapy and remains free of recurrent bladder cancer. Durvalumab 1500 mg will then be administered intravenously once every 3 months to provide an immune boost. Vicinium is administered intravenously (IV) in a 12 week Induction Phase followed by a Maintenance Phase for at least one year with an option for a total of up to 2 years of treatment. During the Maintenance Phase, Vincinium is administered every other week. The dose of Vincinium 30mg in 50 mL of saline.

The purpose of this study is to evaluate the activity of intravesical (instilled directly into the bladder) administration of CG0070 (a type of immunotherapy) and intravenous (IV) administration of Pembrolizumab (Keytruda, a type of immunotherapy) in patients confirmed non-muscular invasive bladder cancer (NMIBC) who have Bacillus-Calmette-Guerin (BCG, a type of immunotherapy) unresponsive disease. This study has 1 arm: CG0070 will be administered intravesically (IVE) following a sequence of bladder washes with 5% DDM (an enhancing agent) and normal saline. CG0070 will be administered weekly for 6 weeks. If the patient shows persistent high-grade disease at Week 12, the patient will receive another cycle of 6 weekly treatments. If there is no disease present at Week 12 (e.g., complete response) then the patient will receive 3 weekly treatments. Pembrolizumab will be given intravenous (IV) at the same time as the CG0070, starting on Day 1 and continue every 3 weeks for up to 2 years.

This study is being done to see how well two drugs (enfortumab vedotin, a type of targeted therapy, and pembrolizumab, a type of immunotherapy) work together, alone, or with platinum chemotherapy to treat patients with urothelial cancer. The study will compare these drugs to other drugs that are usually used to treat this cancer (standard of care). The patients in this study will have cancer that has spread from their urinary system to other parts of their body (metastatic cancer). This study has 3 arms: Arm A: Enfortumab vedotin (Padcev) + Pembrolizumab (Keytruda) Enfortumab vedotin administered as an intravenous (IV) infusion in clinic on days 1 and 8 of every 21 day cycle + Pembrolizumab administered as an IV infusion on day 1 of every 21 day cycle. Arm B: Gemcitabine + cisplatin or carboplatin Cisplatin administered as an IV infusion on day 1 of every 21 day cycle OR Carboplatin dosed according to local guidelines and will be administered as an IV infusion on day 1 of every 21 day cycle + Gemcitabine administered as an IV infusion on days 1 and 8 of every 21 day cycle. Arm C: Enfortumab vedotin + pembrolizumab + Cisplatin or carboplatin Enfortumab vedotin administered as an intravenous (IV) infusion in clinic on days 1 and 8 of every 21 day cycle + Pembrolizumab administered as an IV infusion on day 1 of every 21 day cycle + Cisplatin administered as an IV infusion on day 1 of every 21 day cycle OR Carboplatin dosed according to local guidelines and will be administered as an IV infusion on day 1 of every 21 day cycle

This is a Phase I/Phase II study. Phase 1 will be conducted in BCG-unresponsive (a type of chemotherapy given directly in the bladder) patients with non-metastatic invasive bladder cancer (NMIBC) to establish the safety of durvalumab (Imfinzi, a type of immunotherapy) given:

1. alone

2. in combination with BCG

3. in combination with external beam radiation therapy (EBRT)



Provided safety is demonstrated, the study will proceed to phase 2 testing. Phase 2 will be conducted in the BCG-relapsing (meaning the cancer returns after treatment with BCG) NMIBC population. In phase 2, BCG-relapsing NMIBC subjects will be randomized to treatment with:

1. intravesical (directly in the bladder) BCG in combination with durvalumab

2. durvalumab in combination with radiation (EBRT)

3. retreatment with intravesical BCG alone



In addition to providing additional safety data on the combination regimens studied, phase 2 will provide preliminary information on effectiveness for BCG-relapsing NMIBC subjects.

Durvalumab is given intravenously (IV) in clinic. BCG is instilled (infused) directly in to the bladder in clinic. Frequency of visit dates will vary depending on which treatment arm you are assigned to.

This study will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body.

The study will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI, immunotherapy). Some CPIs have been approved by the FDA for the treatment of urothelial cancer. The study will test if the cancer shrinks with treatment (effectiveness). The study will also look at the side effects of the drug (safety).

Patients will receive enfortumab vedotin intravenously (IV, given in clinic) on days 1, 8 and 15 of every 28 day cycle.

A study investigating the safety and effectiveness of intravesical (instilled directly into the bladder) gemcitabine/docetaxel (Gemzar/Taxotere, both types of chemotherapy) for bacillus Calmette-Guerin (BCG, a type of immunotherapy)-naïve patients with non-muscle invasive bladder cancer (NMIBC). All participants will receive an induction course of gemcitabine/docetaxel instillations followed by maintenance instillations if initial effectiveness is seen. This study has 1 arm: Intravesical Gemcitabine/Docetaxel 1gram gemcitabine in 50ml sterile water; instilled once weekly for 6 weeks and then once monthly for ≤ 21 months. 37.5mg docetaxel in 50ml normal saline solution (NSS); instilled once weekly for 6 weeks and then once monthly for ≤ 21 months.

This randomized phase II trial studies how well cisplatin (a type of chemotherapy) and gemcitabine hydrochloride (a type of chemotherapy) with or without ATR kinase inhibitor VX-970 (a type of targeted therapy) works in treating patients with urothelial cancer that has spread to other places in the body (metastatic disease). Drugs used in chemotherapy, such as cisplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. ATR kinase inhibitor VX-970 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if cisplatin and gemcitabine hydrochloride work better alone or with ATR kinase inhibitor VX-970 in treating patients with urothelial cancer. The study has 2 arms: Arm A: VX-970 + gemcitabine hydrochloride + cisplatin; 1 cycle = 21 days Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, and cisplatin IV over 60 minutes on day 1. Patients also receive ATR kinase inhibitor VX-970 IV over 60 minutes on days 2 and 9. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm B: Gemcitabine hydrochloride + cisplatin; 1 cycle = 21 days Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

This study will be conducted in adult subjects diagnosed with any form of an advanced or metastatic solid tumors including urothelial carcinoma for which standard therapy is no longer effective or is intolerable. This is a study designed to assess safety and tolerability of IK-175 (a type of targeted therapy). All subjects will receive study drug. Subjects will be administered a single dose of IK-175 orally (by mouth or po) during a run-in period and then 21-day treatment cycles of IK-175. Dose level will be detailed by your treating physician.

This is a Phase 3 placebo-controlled study to evaluate the effectiveness of giving an oral targeted FGFR1-3 inhibitor, infigratinib (a type of targeted therapy), as treatment following surgery in adult subjects with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations, who have disease that is considered at high risk for recurrence with surgery alone. The study enrolls subjects with either bladder cancer post radical cystectomy (surgical removal of the bladder) or upper tract urothelial cancer post distal ureterectomy (surgical removal of the ureter) and/or nephrectomy (surgical removal of the kidney). Study treatment is randomized between infigratinib or placebo with treatment until disease recurrence. This study has 2 treatment arms: Arm A: Infigratinib 125 mg Participants will be randomly assigned (1:1) to receive oral infigratinib administered once daily by mouth for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks. Arm B: Placebo Participants will be randomly assigned (1:1) to receive oral placebo administered once daily by mouth for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks.

The primary purpose of this expanded access program is to evaluate the safety and tolerability of enfortumab vedotin (EV, a type of immunotherapy) in participants with locally advanced or metastatic urothelial carcinoma (UC) who have exhausted standard of care therapies and are not eligible to participate in an ongoing EV clinical study. This program will also evaluate the effectiveness of EV. All participants receive treatment: Enfortumab vedotin (EV) is administered intravenously (IV) once weekly for the first 3 weeks of every 4-week cycle (on days 1, 8, and 15)

The purpose of this study is to test the safety of an investigational drug called CFI-402411 (a type of targeted therapy) alone and in combination with pembrolizumab (Keytruda, a type of immunotherapy) and to study its effects in patients with advanced solid tumors (including bladder and kidney cancer) who have progressed following previous therapies. This study has 2 treatment arms: Arm A: CFI-402411 alone CFI-402411 is administered orally (po or by mouth) once daily. The starting dose is 80 mg/day. Specific dose will be provided by your treating physician. Arm B: CFI-402411 + pembrolizumab CFI-402411 is administered orally (po or by mouth) once daily. The starting dose is 80 mg/day. Specific dose will be provided by your treating physician. Pembrolizumab will be given at, 200 mg administered as an intravenous (IV) infusion over 30 minutes every 3 weeks.

This is a Phase 2, multicenter, randomized, open-label study evaluating the safety and effectiveness of trilaciclib (Cosela, a drug that prevents bone marrow suppression caused by chemotherapy) administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab (Bavencio, a type of targeted therapy) maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy in patients receiving first-line treatment for advanced/metastatic bladder cancer. This study has 2 treatment arms: Arm A: Platinum-based chemotherapy followed by avelumab maintenance therapy Gemcitabine administered intravenously (IV) on Day 1 and Day 8 of each 21-day cycle PLUS Cisplatin administered IV on Day 1 of each 21-day cycle OR Carboplatin administered IV on Day 1 of each 21-day cycle FOLLOWED BY Avelumab will be administered IV on Day 1 of each 14-day maintenance cycle Arm B: Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy Trilaciclib administered IV prior to chemotherapy and avelumab maintenance therapy on each day chemotherapy and avelumab maintenance therapy is administered. The chemotherapy and avelumab dosing are the same as in Arm A.

This Phase 3, multinational, single-arm, multicenter study will evaluate the effectiveness and safety of UGN-102 (mitomycin, a type of chemotherapy) as primary therapy in patients with low grade intermediate risk non-muscle-invasive bladder cancer (LG IR NMIBC). UGN-102 consists of mitomycin (a type of chemotherapy) and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration (with a catheter, directly into the bladder) of mitomycin as a liquid, with subsequent conversion to a semi-solid gel depot following instillation into the bladder. This study has 1 treatment arm: Arm A: UGN-102 Patients will receive 6 once-weekly intravesical (directly into the bladder) instillations of UGN-102. The UGN-102 admixture for intravesical instillations contains 75 mg mitomycin.

The primary purpose of this study is to investigate the safety and tolerability and to determine the maximum tolerated dose of DS-1062a (Datopotamab Deruxtecan, a type of targeted therapy). It is the first time the drug has been used in humans. All subjects will receive treatment. DS-1062a is given intravenously (IV) in clinic. Dosing and schedule will be provided by the treatment team.

A Global Study to Determine the Effectiveness and Safety of Durvalumab (a type of immunotherapy) in combination with Tremelimumab (a type of immunotherapy) and Enfortumab Vedotin (a type of targeted therapy) or Durvalumab in Combination With Enfortumab Vedotin for Perioperative (around the time of surgery) Treatment in Patients Ineligible for Cisplatin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer This study has 3 treatment arms: Arm A: Durvalumab + Tremelimumab + Enfortumab vedotin Participants will receive 3 preoperative 21-day cycles of Durvalumab + Tremelimumab + Enfortumab Vedotin, followed by radical cystectomy, followed by 1 cycle of postoperative Tremelimumab and 9 cycles of Durvalumab. Each postoperative cycle is 28 days. Durvalumab 1500 mg by intravenous (IV) infusion given on Day 1 of each cycle. Tremelimumab 75 mg by intravenous (IV) infusion given on Cycle 1 Day 1 and Cycle 2 Day 8 preoperatively and on Cycle 1 Day 1 postoperatively. Enfortumab Vedotin 1.25 mg/kg by intravenous (IV) infusion given on Days 1 and 8 of each 21-day cycle Arm B: Durvalumab + Enfortumab vedotin Participants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin, followed by radical cystectomy, followed by 9 cycles of Durvalumab. Each postoperative cycle is 28 days. Durvalumab 1500 mg by intravenous (IV) infusion given on Day 1 of each cycle. Enfortumab Vedotin 1.25 mg/kg by intravenous (IV) infusion given on Days 1 and 8 of each 21-day cycle Arm C: Straight to cystectomy Radical cystectomy alone. Participants receive standard of care surgery alone.

This is a single arm, Phase II trial involving the use of atezolizumab (Tecentriq, a type of immunotherapy) plus platinum (a type of chemotherapy) and etoposide (a type of chemotherapy) for patients with locally advanced urothelial cancer. The primary goal of this trial is to assess the pathologic complete response rate (meaning there is no longer any cancer visible on imaging scans) at time of cystectomy (the surgical removal of the bladder) in patients after being treated with a combination therapy of atezolizumab, platinum, and etoposide. The study population will include male and female patients over the age of 18 with invasive small cell / neuroendocrine carcinoma of the bladder, with or without urothelial cancer component, who are eligible for platinum based chemotherapy and immunotherapy. All patients will be fit to undergo surgical resection of their cancer by cystectomy. This study has 1 treatment arm: Atezolizumab with Platinum and Etoposide, followed by cystectomy. Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of every 21 day cycle (1 cycle = 21 days), with chemotherapy, for 4 cycles. Following cystectomy, Atezolizumab maintenance will continue once every 21 days for up to 1 year. Chemotherapy will include Etoposide given IV on Days 1 - 3 every cycle for the first 4 cycles. Chemotherapy will include either Carboplatin given IV on Day 1 every cycle for the first 4 cycles OR Cisplatin given IV on Day 1 every cycle for first 4 cycles. Cystectomy should be performed within 42 days after completion of last administered study therapy of induction phase (first 4 cycles of chemotherapy). Cystectomy should be performed within 42 days after completion of last administered study therapy (after the first 4 cycles of Atezolizumab + chemotherapy).

To evaluate the activity of intravesical (IVE) administration of CG0070 (a type of immunotherapy) in patients with confirmed non-muscular invasive bladder cancer (NMIBC) who have Bacillus-Calmette-Guerin (BCG) unresponsive disease that has not metastasized outside the bladder. This study only has 1 treatment arm: CG0070 will be administered intravesically (IVE, directly into the bladder) following a sequence of bladder washes. CG0070 will be administered weekly for 6 weeks. If the patient has persistent high-grade disease at Week 13, the patient will receive another cycle of 6 weekly treatments. If there is no disease present at Week 13 (e.g. complete response) then the patient will receive 3 weekly treatments. Beginning at Week 25, patients will receive weekly treatments every 12 weeks for 26 weeks, then every 24 weeks thereafter.

This phase II trial studies the effect of adding pembrolizumab (Keytruda, a type of immunotherapy) to gemcitabine (Gemzar, a type of chemotherapy) in treating patients with non-muscle invasive bladder cancer whose cancer does not respond to Bacillus Calmette-Guerin (BCG) treatment. Chemotherapy drugs, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the patient's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding pembrolizumab to gemcitabine may delay the return of BCG-unresponsive bladder cancer for longer period compared to gemcitabine alone. This study has 1 treatment arm: INDUCTION: Patients receive pembrolizumab intravenously (IV) over 25-40 minutes on day 1 of cycles 1-4. Patients also receive gemcitabine hydrochloride intravesically (IVE, directly into the bladder) on days 1, 8 and 15 of cycles 1 and 2. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning at cycle 5, patients with no evidence of disease after induction receive pembrolizumab IV over 25-40 minutes and gemcitabine intravesically on day 1. Treatment repeats every 3 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity.

This phase III trial compares the effect of adding durvalumab (Imfinzi, a type of immunotherapy) to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone. This study has 3 treatment arms: Arm A: Durvalumab + chemotherapy Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Arm B: Chemotherapy Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Arm C: Durvalumab + Gemcitabine Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

This is a Phase 1, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, preliminary antitumor activity, and effects of XL092 (a type of targeted therapy) administered alone, in combination with atezolizumab (Tecentriq, a type of immunotherapy), and in combination with avelumab (Bavencio, a type of immunotherapy) to subjects with advanced solid tumors. This study has 3 treatment arms: Arm A: XL092 alone XL092 will be given orally (by mouth or PO). Dosage and dosing schedule to be provided by treatment team. Arm B: XL092 + Atezolizumab XL092 will be given orally (by mouth or PO). Dosage and dosing schedule to be provided by treatment team. Atezolizumab is administered as a 1200 mg IV (intravenously) infusion once every 3 weeks. Arm C: XL092 + Avelumab XL092 will be given orally (by mouth or PO). Dosage and dosing schedule to be provided by treatment team. Avelumab is administered as an 800 mg IV infusion once every 2 weeks.