Bladder Cancer Trials

The study will evaluate the clinical activity of PD-(L)1 Checkpoint Inhibitor regimens (immunotherapy) in combination with the investigational agent sitravatinib (a type of targeted therapy) in patients with advanced or metastatic urothelial carcinoma. This study has 2 potential treatment arms: Arm A: Sitravatinib + Nivolumab (Opdivo, a type of immunotherapy) Nivolumab over 30 min intravenously (IV) infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally (po or by mouth) once per day continuously in 28-day cycles. Arm B: Sitravatinib + Pembrolizumab (Keytruda, a type of immunotherapy) + Enfortumab vedotin (Padcev, a type of immunotherapy) Pembrolizumab 200 mg over 30 min IV infusion every 3 weeks, sitravatinib orally once per day continuously in 21-day cycles (at 35 mg, 50 mg, 70 mg, or 100 mg) and enfortumab vedotin over 30 min IV infusion on Day 1 and Day 8 in 21-day cycles (at 1 mg/kg or 1.25 mg/kg).

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.

This is a clinical trial studying the administration of NanoDoce (docetaxel, a type of chemotherapy) as a direct injection to the bladder wall immediately after tumor resection and as an intravesical instillation (put directly in to the bladder using a catheter). All participants will receive NanoDoce, and will be evaluated for safety and tolerability, as well as the potential effects of NanoDoce on urothelial carcinoma. There are 2 treatment cohorts: Cohort 1: Non-Muscle Invasive Bladder Cancer Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT). Visit 2 instillation, all subjects will receive an initial intravesical instillation within 2 hours of direct injection. Induction and Maintenance Instillations, all subjects will receive intravesical instillations in an Induction Period (6 weekly NanoDoce intravesical instillations, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations, followed by 9 weeks of rest). Cohort 2: Muscle Invasive Bladder Cancer Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT). Visit 2 instillation, all subjects will receive an initial intravesical instillation within 2 hours of direct injection. Subjects will then receive standard of care therapy.

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).

A study to evaluate Nivolumab (Opdivo) or Nivolumab Plus Experimental Medication BMS-986205 with or without BCG (Bacillus Calmette–Guérin, a type of chemotherapy instilled directly in to the bladder) in BCG-Unresponsive non-muscle invasive Bladder Cancer. This study has 4 arms: dosing of each drug and combination will be given at time of enrollment. Arm A: Nivolumab monotherapy Arm B: Nivolumab + BCG Arm C: Nivolumab + BMS-986205 Arm D: Nivolumab + BMS-986205 + BCG

This is a randomized phase 2 trial of gemcitabine (a type of chemotherapy) + carboplatin (a type of chemotherapy) + nivolumab (a type of immunotherapy) or gemcitabine + oxaliplatin (a type of chemotherapy) + nivolumab for the treatment of cisplatin-ineligible patients with metastatic urothelial cancer. Randomization will be stratified on the metastasis status (lymph node only vs. other metastatic sites). This study has 2 arms: dosing schedule will be given at time of enrollment. Both treatment arms will receive up to 6 cycles of combination therapy. Patients with at least stable disease at the completion of 6 cycles of treatment may continue "maintenance" single agent nivolumab for up to 24 cycles. Patients who require discontinuation of chemotherapy (i.e., gemcitabine plus carboplatin or gemcitabine plus oxaliplatin) prior to Cycle 6, but who have at least stable disease, may be considered for ongoing treatment with single-agent nivolumab on the "maintenance" phase after discussion with the sponsor-investigator. Arm A: Gemcitabine plus carboplatin plus nivolumab Gemcitabine is given intravenously (IV) at 1000 mg/m2. Carboplatin is given IV at AUC 4.5 (based on the Calvert formula). Nivolumab is given IV at 240 mg. Arm B: Gemcitabine plus oxaliplatin plus nivolumab Gemcitabine and nivolumab will be given the same as in Arm A. Oxaliplatin is given IV at 130 mg/m2.

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 randomized phase III trial studies how well pembrolizumab (a type of immunotherapy) works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes (metastatic). Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Patients will be randomized to one of two arms:

Arm A Observation

Patients undergo observation only (no treatment).

Arm B Pembrolizumab

Patients receive pembrolizumab by intravenous (IV, in clinic) infusion over 30 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

This is a phase II trial designed to estimate the activity of single agent tremelimumab (a type of immunotherapy) in subjects with metastatic urothelial cancer with disease progression despite prior treatment with PD-1/PD-L1 blockade. This study has 1 arm: Tremelimumab: Tremelimumab 750 mg given intravenously (IV) on Day 1 of each 28 day cycle; up to 7 cycles. Subjects that complete all initial 7 cycles but later progress during follow up may receive an additional 7 cycles of tremelimumab providing they meet eligibility criteria.

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 randomized, open-label, controlled, multi-center, global Phase III study to determine the effectiveness and safety of combining durvalumab (a type of immunotherapy) ± tremelimumab (a type of immunotherapy) with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra). This study has 3 treatment arms; all treatments are given in clinic. Standard of care (SoC) chemotherapy regimens are given following local clinic and provider orders. Arm A: Durvalumab in Combination with SoC Chemotherapy Durvalumab given intravenously (IV) every 3 weeks with SoC chemotherapy, followed by durvalumab monotherapy every 4 weeks. All patients will receive one of the following standard of care (SoC) chemotherapy regimens every 3 weeks for 6 cycles: • cisplatin+ gemcitabine • If the patient is cisplatin-ineligible, carboplatin + gemcitabine Arm B: Durvalumab in Combination with Tremelimumab + SoC Chemotherapy Durvalumab and Tremelimumab given intravenously (IV) every 3 weeks with SoC chemotherapy, followed by durvalumab given alone every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care (SoC) chemotherapy regimens every 3 weeks for 6 cycles: • cisplatin+ gemcitabine • If the patient is cisplatin-ineligible, carboplatin + gemcitabine Arm C: SoC Chemotherapy Patients will receive one of the following standard of care (SoC) chemotherapy regimens every 3 weeks for 6 cycles: • cisplatin+ gemcitabine • If the patient is cisplatin-ineligible, carboplatin + gemcitabine

A multi center, open-label, Phase 1 dose escalation study with expansion cohort is designed to determine the maximum tolerated dose, recommended phase II dose, and dosing schedule of PRS-343 (a type of targeted therapy) in patients with HER2+ advanced or metastatic solid tumors, including bladder cancer. PRS-343 will be administered by intravenous (IV) infusion every 3 weeks initially. If safety data suggest a different dosing schedule should be evaluated, dosing every 2 weeks or every 4 weeks in a 28-day cycle may be conducted.

CRLX101 consists of a sugar molecule cyclodextrin linked to a chemotherapy drug called camptothecin. The combined molecule or nanoparticle drug travels through the blood. Once inside cancer cells, the chemotherapy drug is released from the molecule. Olaparib (a type of targeted therapy, a PARP inhibitor) is a drug that may stop cancer cells from repairing the DNA damage caused by chemotherapy. Researchers want to see how safe it is to give CRLX101 and olaparib together and to see how well the combination treats specific types of cancer. Patients will receive the two study drugs in 28 day cycles (1 cycle = 28 days). CRLX 101 will be given intravenously (IV) on days 1 and 15 and the olaparib will be taken by mouth days 3-13 and 17-26.

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 single arm Phase II study with a safety run-in to identify the recommended phase II dose of the combination therapy of atezolizumab (Tecentriq, a type of immunotherpy) and guadecitabine (a type of immunotherpay). Patients with recurrent/advanced urothelial carcinoma (stage IV) who had previously progressed on check-point inhibitor therapy (immunotherapy) with PD-1 or PD-L1 targeting agents are eligible for this study. After a dose that is safe and tolerable has been established, a dose expansion phase (Phase II) will begin. This study has 1 arm: Atezolizumab + Guadecitabine Patients will be administered atezolizumab intravenously on day 1 and day 22 of a 6 week cycle for 8 cycles. Guadecitabine will be administered subcutaneously (an injection into the fat just below the skin) on days 1 through 5 of the 6 week cycle for 4 cycles.

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 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).

The purpose of this study is to evaluate the safety and pharmacokinetics of enfortumab vedotin (Padcev, a type of immunotherapy) as well as assess the immunogenicity (the effect on the immune system) and antitumor activity in subjects with metastatic urothelial that express Nectin-4. All subjects will receive a single 30 minute intravenous (IV) infusion of enfortumab vedotin once weekly for the first 3 weeks of every 4 week cycle (i.e., on Days 1, 8 and 15). Specific dosing will be provided by your treating physician.

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.

A global study to evaluate peri-operative (both before and after surgery) pembrolizumab (Keytruda, a type of immunotherapy) with chemotherapy versus placebo plus chemotherapy in cisplatin (a type of chemotherapy) eligible patients. The study has 2 arms: Arm A: Pembrolizumab + Gemcitabine + Cisplatin + Surgery Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab. Pembrolizumab 200 mg given by intravenous (IV) infusion on Day 1 of each 21-day cycle, plus Gemcitabine 1000 mg/per meter squared (based on height and weight), given by IV infusion on Days 1 and 8 of each 21-day cycle, plus Cisplatin 70 mg/per meter squared, given by 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: Placebo + Gemcitabine + Cisplatin + Surgery Participants received 4 preoperative cycles of placebo PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative placebo to pembrolizumab. Regimen is given the same as above, using placebo instead of pembrolizumab.

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.

The purpose of this study is to evaluate efficacy of erdafitinib (a type of targeted therapy) versus chemotherapy or pembrolizumab (a type of immunotherapy) in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations (a particular genetic mutation in cancer cells) who have progressed after one prior treatment. It will consist of screening, treatment phase, and post-treatment follow-up. The study has 2 treatment arms: 1 cycle = 21 days Arm A: for participants treated with prior immunotherapy Erdafitinib + Vinflunine OR Docetaxel (both are types of chemotherapy) Erdafitinib tablets are taken by mouth (orally or PO) at a dose of 8 mg, once daily. Vinflunine 320 mg/m2 is given as a 20 minute intravenous (IV) infusion once every 3 weeks. Docetaxel 75 mg/m2 is given as a 1 hour IV infusion every 3 weeks. Treatment with either agent is the choice of the treating physician. Arm B: for participants NOT treated with prior immunotherapy Erdafitinib + Pembrolizumab Erdafitinib tablets are taken by mouth at a dose of 8 mg, once daily. Pembrolizumab 200 mg as a 30 minute IV infusion once every 3 weeks.