Bladder Cancer Trials

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 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).

In this four part study, NKTR-214 (a type of immunotherapy) will be administered in combination with nivolumab (Opdivo, a type of immunotherapy) in Parts 1 & 2, and with nivolumab and ipilimumab (Yervoy, a type of immunotherapy) in Parts 3 & 4. In Part 1, the safety, effectiveness and recommended dose of NKTR-214 in combination with nivolumab will be determined. In Part 2, the clinical benefit, safety, and tolerability of combining NKTR-214 with nivolumab Renal Cell Carcinoma and Urothelial Carcinoma. In Part 3, the safety, effectiveness and dose level of NKTR-214 in combination with nivolumab and ipilimumab will be determined. In Part 4, the clinical benefit, safety, and tolerability of the combination of all three drugs will be evaluated in select patients with renal cell carcinoma. All three drugs target the immune system and may act together to promote anti-cancer effects. This study has 2 arms: All drugs are given intravenously (IV) in clinic. Arm A: Combination of NKTR-214 + nivolumab Part 1: Patients with select tumor types will receive NKTR-214 doses administered either once every 2 weeks or once every 2 weeks, in combination with 360 mg of nivolumab once every 3 weeks or 240 mg nivolumab once every 2 weeks. Part 2: Additional patient cohorts with select tumor types will be dosed at the dose/schedule of NKTR-214 and nivolumab (as determined by Part 1 of the trial). Arm B: Combination of NKTR-214 + nivolumab + ipilimumab Part 3: The first schedule to be evaluated, Cohort A, is NKTR-214 0.006 mg/kg and nivolumab 360 mg once every 3 weeks with the addition of ipilimumab 1 mg/kg (kilogram, based on your weight) once every 6 weeks. Upon review of safety, tolerability, and other data collected in Cohort A, alternative doses/schedules may be considered where ipilimumab will be administered at a later cycle. Part 4: Additional patient cohorts with select tumor types will be dosed at the dose/schedule of NKTR-214 in combination with nivolumab and ipilimumab (as determined by Part 3 of the trial).

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.

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 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.

The purpose of this study is to measure the effect of IPI-549 (a type of targeted therapy) in combination with nivolumab (Opdivo, a type of immunotherapy) when compared to nivolumab monotherapy in advanced urothelial cancer patients who have progressed or recurred following treatment with platinum-based chemotherapy. Eligible patients who have confirmed progression of disease during treatment with nivolumab monotherapy may crossover to the combination treatment arm. The study has 2 arms: all cycles are 28 days Arm 1: IPI-549 + Nivolumab Participants receive IPI-549 40mg taken by mouth (PO) once daily in combination with nivolumab 480 mg given intravenously (IV) once every 4 weeks Arm 2: Placebo + Nivolumab Participants receive placebo taken by mouth (PO) once daily in combination with nivolumab 480 mg given intravenously (IV) once every 4 weeks

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.

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).

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 aim of this study is to evaluate a risk-adapted approach to the treatment of muscle invasive bladder cancer. Each baseline transuretheral resection of bladder tumor (TURBT) sample will be sequenced while proceeding with neoadjuvant (prior to surgery) accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) chemotherapy. All of these drugs are types of chemotherapy. Based on the mutational profile and the post AMVAC TURBT findings, patients will be treated with active surveillance (experimental arm), or standard of care intravesicle (directly in the bladder) therapy, chemoradiation (chemotherapy + radiation) or surgery. We hypothesize that this approach will lead to non-inferior metastasis-free survival at 2 years, while preserving the bladder and thus quality-of-life for a proportion of patients. Patients on each arm of this study will have a TURBT procedure (TURBT #1), followed by MVAC chemotherapy. Each drug (methotrexate, vinblastine, doxorubicin and cisplatin) will be given intravenously (IV) on days 1 and 14 of each 28 day cycle for 3 cycles. Patient will then have a second TUBRT procedure (TRUBT #2). Patients will then receive 1 of 4 possible arms: Arm A: Chemoradiation followed by TURBT #3 Radiation: Intensity modulated radiation therapy (IMRT) 2.0 Gy per fraction to the whole bladder plus a margin for a total of 32 fractions (64.0 Gy). Radiation will be administered once daily from Monday to Friday. Chemotherapy: 5-FU (Fluorouracil) given continuously for 24 hours via intravenous infusion days 1-5 and 16-20 with radiation treatment + Mitomycin C given intravenously (IV) on day 1 only, with radiation treatment. Arm B: Active surveillance Patients will receive standard of care surveillance for recurrence of their bladder cancer. Arm C: Intravesicle therapy followed by TURBT#3 Patients will receive standard of care/provider preference intravesicle therapy. Arm D: Radical cystectomy Patients will receive standard of care radical cystectomy (complete surgical removal of the bladder).

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.

This pilot phase II trial studies how well sapanisertib (a type of targeted therapy) works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic) with tuberous sclerosis (TSC)1 and/or TSC2 mutations (changes in deoxyribonucleic acid [DNA]). Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The study has 1 arm: Sapanisertib Patients receive sapanisertib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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 randomized phase III trial studies Tokyo-172 strain bacillus Calmette-Guerin (BCG) solution with or without a vaccination using Tokyo-172 strain BCG to see how well it works compared with TICE BCG solution in treating patients with bladder cancer that has not spread to muscle. BCG is a non-infectious bacteria that when instilled into the bladder may stimulate the immune system to fight bladder cancer. Giving different versions of BCG with vaccine therapy may prevent bladder cancer from returning. The study has 3 arms: Arm I: BCG solution (standard of care) INDUCTION: Patients receive TICE BCG solution intravesically (directly in the bladder) once a week for 6 weeks. MAINTENANCE: Patients receive TICE BCG solution intravesically once a week for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 for up to 7 doses. Arm II: Tokyo-172 strain BCG solution INDUCTION: Patients receive Tokyo-172 strain BCG solution intravesically once a week for 6 weeks. MAINTENANCE: Patients receive Tokyo-172 strain BCG solution once a week for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 for up to 7 doses. Arm III: Tokyo-172 strain BCG solution with priming (priming may help treatment work better) PRIME: Patients receive Tokyo-172 strain BCG vaccine once intradermally (injected just under the top layers of skin). INDUCTION: Within 21 days, patients receive Tokyo-172 strain BCG solution as in Arm II. MAINTENANCE: Patients receive Tokyo-172 strain BCG solution as in Arm II.

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.

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 evaluate the safety, dose, immune effect and early clinical activity of GRT-C901 and GRT-R902, a personalized cancer vaccine (a type of immunotherapy), in combination with nivolumab (Opdivo, a type of immunotherapy) and ipilimumab (Yervoy, a type of immunotherapy), in patients with metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, gastroesophageal adenocarcinoma, and metastatic urothelial cancer. This vaccine regimen uses two vaccines as a prime/boost approach (GRT-C901 first followed by GRT-R902) to stimulate an immune response. All participants receive both vaccines (given by intramuscular, or IM injection), nivolumab (given intravenously or IV) and ipilimumab (given IV). Doses and dosing schedule will be provided by treatment team.

The primary purpose of this study is to evaluate the tolerability and safety profile of ASP8374 (a type of immunotherapy) when administered as a single agent and in combination with pembrolizumab (Keytruda, a type of immunotherapy) in participants with locally advanced (unresectable) or metastatic solid tumor malignancies. The secondary purpose of this study is to evaluate the anti-tumor effect, duration of response, persistence of response after discontinuation, and disease control rate of ASP8374 when administered as a single agent and in combination with pembrolizumab. This study has 2 arms: Arm A: ASP8374 Participants will be enrolled in the escalation cohorts or expansion cohorts and receive ASP8374 (monotherapy) intravenously on Day 1 of every 3-week cycle (up to a maximum of 8 dose strengths). Arm B: ASP8374 and pembrolizumab Participants will be enrolled in the escalation cohorts or expansion cohorts and receive ASP8374 and pembrolizumab (combination therapy) intravenously on Day 1 of every 3-week cycle (up to a maximum of 5 dose strengths of ASP8374 and one fixed dose strength of pembrolizumab).

This is a single arm open label multi-institutional phase II trial of olaparib (a type of targeted therapy, a PARP inhibitor) monotherapy in subjects with metastatic urothelial cancer that has DNA damage response (DDR) alterations (specific genetic changes in the tumor cells). The primary objective of the study is to estimate the objective response rate (measurable on radiographic imaging) to treatment with olaparib. The study has 1 arm: Olaparib monotherapy (olaparib only). Each cycle is 28 days. Olaparib is taken by mouth (orally or PO) at either 300 mg or 200 mg twice daily, based on kidney function tests.

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.