Bladder Cancer

Researchers are evaluating a new PET imaging tracer called [18F]FAPI-74 to detect cancer by targeting the fibroblast-activation protein (FAP) found in cancer-associated fibroblasts. This study aims to compare [18F]FAPI-74 PET scans to the standard [18F]-FDG PET scans and other imaging methods like CT or MRI across several cancers including pancreatic ductal adenocarcinoma, cholangiocarcinoma, hepatocellular carcinoma, gastric, bladder, ovarian cancers, pheochromocytoma/paraganglioma, small cell lung cancer, neuroendocrine cancer, mesothelioma, and sarcoma. The study is a phase 2 interventional trial conducted by the National Cancer Institute (NCI). Participants will receive an intravenous dose of [18F]FAPI-74 before undergoing PET/CT imaging about one hour later. They will also have a baseline FDG PET scan within one week. If tumors are detected by [18F]FAPI-74, additional scans using this tracer and FDG may be repeated during routine treatment and if cancer progresses within two years. Those with negative baseline [18F]FAPI-74 scans will not have repeated scans but remain in follow-up. The study involves a single arm where participants undergo both types of PET imaging. During the study, participants will have scans at baseline and potentially at subsequent treatment or progression points. Safety monitoring includes observation for reactions to the tracer up to three days after injection. Researchers will measure the mean number of lesions, standardized uptake values at baseline, post-treatment, and recurrence. Follow-up calls will continue for two years to assess progression-free survival and overall survival. The total participation duration includes imaging visits and two years of follow-up monitoring.

Researchers are studying men with metastatic castration-resistant prostate cancer (mCRPC) to understand how different PET/CT scans can predict outcomes during radioligand therapy with 177Lu-PSMA-617. This is an exploratory, prospective study conducted at a single center, focusing on imaging tumor heterogeneity to help assess therapy effects and patient response. The study is designed specifically for Veterans undergoing this treatment. Participants will receive several types of PET/CT scans at different times: before starting LuPSMA radioligand therapy (RLT), and then after the 2nd, 4th, and 6th treatment cycles. These scans include 18F-Fluciclovine PET/CT (Axumin), 18F-DCFPyL PET/CT, and 18F-FDG PET/CT. The 18F-Fluciclovine scans will be performed within seven days of the PSMA PET scans to compare imaging results at each time point. During the study, detailed imaging measures such as lesion uptake and tumor volume will be collected and analyzed over time. Patients will be followed at the institution to correlate these imaging results with clinical outcomes. The main outcome measured is the impact of 18F-Fluciclovine PET/CT on predicting outcomes of the 177Lu-PSMA-617 therapy from enrollment through 34 weeks of treatment.

Researchers are evaluating the use of a radiotracer called 64Cu-GRIP B with PET imaging to detect granzyme B, a biomarker produced by immune cells during immunotherapy, in patients with advanced cancers that have spread to nearby tissues or lymph nodes. This phase I/II study focuses on genitourinary cancers, including renal cell carcinoma, urothelial cancer, and metastatic castration-resistant prostate cancer, aiming to assess safety and usefulness of the imaging in monitoring immune response. Participants are divided into four groups based on cancer type: metastatic genitourinary malignancies, renal cell and urothelial carcinoma, metastatic castration-resistant prostate cancer, and other solid tumors. All receive the 64Cu-GRIP B injection followed by PET scans at baseline. Some groups have additional scans at 8 weeks and at disease progression. Imaging methods include PET/CT or PET/MRI, with safety monitoring conducted at multiple time points after tracer injection. During the study, patients undergo scans, blood sampling, and tumor biopsies when applicable. Researchers monitor adverse events, tracer distribution, and tumor uptake patterns over time. Outcomes measured include safety, tracer pharmacokinetics, changes in tumor uptake values, and correlations with clinical outcomes such as response to immunotherapy and progression-free survival. Participants are followed for up to two years to assess long-term effects and disease progression.

Researchers are evaluating the effectiveness of combining 9MW2821 with toripalimab compared to using 9MW2821 alone in patients with locally advanced or metastatic urothelial carcinoma who have not yet received systemic treatment for their advanced cancer. This randomized phase II trial aims to improve first-line treatment options for this condition, which includes urothelial carcinoma of the bladder, renal pelvis, and ureter. Participants will be assigned to receive either the combination of 9MW2821, a nectin-4 antibody-drug conjugate with MMAE payload, plus toripalimab, an anti-PD-1 antibody, or 9MW2821 monotherapy. The study treatments will be given according to protocol, with no masking or blinding. The trial includes a planned 3-year period to assess treatment response and safety. Throughout the study, participants will undergo regular assessments including evaluations of tumor response using RECIST v1.1 criteria, safety monitoring, and immunogenicity tests over three years. Researchers will measure outcomes such as the objective response rate and other efficacy endpoints. Participants must be able to follow study visits, treatment, and laboratory procedures, with contraceptive measures maintained until 180 days after the last dose. The overall participation spans from screening through treatment and follow-up over the study duration.

Researchers are evaluating the safety and effectiveness of combining the drugs 9MW2821 and Toripalimab in patients with urothelial cancer who are undergoing surgery. This phase II clinical trial is open-label and involves multiple centers. The study focuses on patients with confirmed non-metastatic urothelial cancer, including muscle-invasive bladder cancer (MIBC) and high-risk upper tract urothelial carcinoma (UTUC). Participants receive intravenous infusions of 9MW2821 at a dose of 1.25 mg/kg and Toripalimab at 240 mg. The study includes three groups based on cancer type and risk: Arm 1 with MIBC, Arm 2 with high-risk UTUC, and Arm 3 with MIBC. The study is not randomized, and all participants receive the experimental treatment combination. During the study, participants will be monitored for up to 24 months to assess outcomes such as pathological complete response (pCR), clinical complete response (cCR), overall response rate, disease-free survival, progression-free survival, overall survival, and safety events. Researchers will also evaluate immunogenicity and expression of biomarkers Nectin-4 and PD-L1. Regular assessments include tumor tissue testing and organ function monitoring to ensure participant safety and treatment adherence.

Researchers are evaluating the safety, tolerability, effectiveness, pharmacokinetics, and immune response of a combination treatment using 9MW2821 and Toripalimab injections in adults with locally advanced or metastatic urothelial cancer. This phase Ib/II open-label study is conducted at multiple centers to better understand this treatment approach for this advanced cancer type. Participants receive 9MW2821 at doses of 1.0, 1.25, or 1.5 mg/kg by intravenous infusion every cycle, combined with 240 mg of Toripalimab given intravenously every cycle. Treatment continues until the disease progresses or side effects become intolerable. This single-arm trial does not include a comparison group and monitors patients closely during the treatment period. During the study, participants undergo regular assessments including safety monitoring for adverse events up to 24 months. Researchers also measure tumor response, progression-free survival, overall survival, and pharmacokinetics over 12 to 24 months. Participants must provide tumor tissue samples and complete study procedures, with ongoing monitoring of immunogenicity and disease control throughout the trial duration.

Researchers are evaluating the effectiveness, safety, and immune response of a combination treatment of 9MW2821 and Toripalimab compared to standard chemotherapy for adults with locally advanced or metastatic urothelial cancer who have not had prior systemic treatment. This phase 3 randomized, controlled, open-label study involves multiple centers and aims to provide new options for this serious condition. Participants will be randomly assigned to receive either the experimental combination of 9MW2821 at 1.25 mg/kg and Toripalimab at 240 mg, both given by intravenous infusion, or standard chemotherapy consisting of Gemcitabine with either Cisplatin or Carboplatin, also given by intravenous infusion. The study includes two treatment groups and is designed to compare these approaches as first-line therapy. During the study, participants will undergo regular assessments including imaging to measure tumor response using criteria up to 50 months, overall survival tracking, and evaluations of side effects and immune responses. Researchers will monitor progression-free survival and other outcomes, along with safety and tolerability. Follow-up visits and evaluations will be conducted throughout the study period to gather comprehensive data on the treatments' impact and participant health.

Researchers are evaluating MDNA11, a long-acting "beta-only" recombinant interleukin-2 designed to activate immune cells that kill cancer while minimizing activation of immunosuppressive cells. This Phase 1/2 study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with the checkpoint inhibitor pembrolizumab in patients with advanced solid tumors. The study is conducted at multiple sites with regulatory and ethical approvals and includes about 115 patients. The trial has several parts: dose escalation and expansion for MDNA11 monotherapy and for its combination with pembrolizumab. MDNA11 is given intravenously every two weeks with doses adjusted to find the recommended dose for expansion. Tumor assessments using CT or MRI scans happen every 8 weeks to monitor response until disease progression or other study-end criteria occur. Treatment may continue beyond progression under certain conditions. Participants undergo evaluations including tumor imaging, laboratory tests, and safety monitoring over up to 24 months. Researchers measure recommended dose levels, treatment-related adverse events, pharmacokinetics, immune response, and anti-tumor activity such as response rates and progression-free survival. Patients can withdraw anytime, and safety follow-up continues to understand MDNA11's effects alone and with pembrolizumab.

Bladder cancer is a common urinary system cancer, with a significant number of patients diagnosed with non-muscle-invasive bladder cancer (NMIBC). NMIBC varies in risk based on tumor size, stage, and grade, and while surgery is primary treatment, residual tumors and recurrence are concerns, especially for larger tumors. This research aims to explore bladder-sparing treatment strategies for large-volume NMIBC, balancing quality of life with cancer control outcomes. The study compares two approaches: a bladder-sparing set and immediate radical cystectomy. The bladder-sparing method involves neoadjuvant chemotherapy combined with immunotherapy, followed by maximal transurethral resection of bladder tumor (TURBT) and a second TURBT, then mitomycin C bladder instillation therapy. The radical cystectomy group undergoes surgery immediately after three cycles of neoadjuvant therapy. Participants will be monitored from enrollment through three years after treatment, focusing on recurrence-free survival as the main outcome. Progression-free survival is also measured. Regular follow-up will assess tumor status and safety. The study includes adults aged 18 to 80 who can tolerate chemotherapy and immunotherapy and are willing to comply with study requirements, including ongoing evaluations and bladder instillation therapy.

Researchers are evaluating new treatment options for people with high-risk non-muscle invasive bladder cancer (HR NMIBC), a type of bladder cancer that affects the inner lining of the bladder but has not spread to the muscle or beyond. This includes carcinoma in situ (CIS), a flat form of bladder cancer limited to the bladder's surface. The study aims to find out if adding intismeran autogene, an immune system-targeting treatment, to the standard Bacillus Calmette-Guerin (BCG) therapy can improve outcomes for people with HR NMIBC by helping the immune system attack the cancer more effectively. Participants are assigned to different groups. One group receives both intismeran autogene by intramuscular injection every three weeks for nine doses along with BCG treatment given once weekly for six weeks, followed by additional weekly doses at later weeks. Another group receives BCG alone on the same schedule, while a third group receives only intismeran autogene. The study compares these treatments to see if the combination improves survival without cancer growth, spread, or return. During the study, participants will be monitored for up to approximately five years to track event-free survival, recurrence-free survival, overall survival, and other outcomes. Researchers will also evaluate adverse events and treatment tolerability. Follow-up includes assessments at regular intervals to observe disease status and safety. The total participation time may last several years to gather long-term data on treatment effects.