Blood Test and Immunotherapy for Bladder Cancer
Palo Alto (17 mi)Overseen byMatthew D Galsky
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II/III trial examines whether patients who have undergone surgical removal of bladder, but require an additional treatment called immunotherapy to help prevent their bladder cancer from coming back, can be identified by a blood test. Many types of tumors tend to lose cells or release different types of cellular products including their DNA which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. In this study, a blood test is used to measure ctDNA and see if there is still cancer somewhere in the body after surgery and if giving a treatment will help eliminate the cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and relatlimab, can help the body's immune system to attack the cancer, and can interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine if ctDNA measurement in blood can better identify patients that need additional treatment, if treatment with nivolumab prolongs patients' life and whether the additional immunotherapy treatment with relatlimab extends time without disease progression or prolongs life of bladder cancer patients who have undergone surgical removal of their bladder.
Do I need to stop my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on concurrent antineoplastic therapy or immunosuppressive agents, except for certain corticosteroids. It's best to discuss your specific medications with the trial team.
Is the drug used in the trial 'Blood Test and Immunotherapy for Bladder Cancer' a promising treatment?Yes, the drug used in the trial is promising because it is part of a group of drugs called PD-1/PD-L1 inhibitors, which have shown effectiveness in treating advanced bladder cancer. These drugs help the immune system fight cancer cells and have been approved for use in certain cases of bladder cancer, offering hope for improved survival.23489
What safety data exists for Nivolumab, Opdivo, Relatlimab, Opdualag, BMS-986016, or relatlimab-rmbw in bladder cancer treatment?The provided research does not contain specific safety data for Nivolumab, Opdivo, Relatlimab, Opdualag, BMS-986016, or relatlimab-rmbw in the context of bladder cancer treatment. The studies focus on other PD-L1 inhibitors like Durvalumab and MPDL3280A, which have shown favorable safety profiles in bladder cancer. For specific safety data on the mentioned treatments, further research or clinical trial results would be needed.136810
What data supports the idea that Blood Test and Immunotherapy for Bladder Cancer is an effective treatment?The available research shows that immunotherapy, specifically drugs like Nivolumab and others targeting the PD-1/PD-L1 pathway, has been effective in treating advanced bladder cancer. These drugs have been approved by the FDA due to their success in helping some patients with advanced stages of the disease. Although not all patients benefit, those who do have shown significant improvement, which has led to a shift in treatment strategies for bladder cancer. This is especially important as traditional treatments had not improved survival rates significantly over the past decade.357811
Eligibility Criteria
This trial is for adults with bladder cancer who've had their bladders and lymph nodes surgically removed recently. It's not for those who only had part of the bladder taken out or have heart failure, severe hearing loss, bad peripheral neuropathy, or poor overall health. Participants should not have any remaining visible cancer after surgery.Inclusion Criteria
I have moderate heart failure.
I can walk and take care of myself but cannot do any physical work.
My bladder cancer is confirmed and mainly urothelial type, but may include other cell types.
I have moderate to severe numbness, tingling, or pain in my hands or feet.
I have bladder cancer and haven't had cisplatin before surgery. I can't have cisplatin after surgery either.
I have moderate to severe hearing loss.
Treatment Details
The study tests if DNA from tumor cells in blood can guide immunotherapy post-bladder removal surgery. It uses a test called Signatera to detect this DNA and then treats patients with nivolumab alone or combined with relatlimab to prevent cancer recurrence.
4Treatment groups
Experimental Treatment
Active Control
Group I: Cohort B, Arm IV (ctDNA surveillance, nivolumab)Experimental Treatment7 Interventions
Patients in Cohort B, Arm IV undergo ctDNA surveillance consisting of collection of tissue and blood during screening and collection of blood only on study and during follow up. Patients who convert to ctDNA(+) during surveillance then receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans throughout the trial.
Group II: Cohort A, Arm II (nivolumab, relatlimab)Experimental Treatment7 Interventions
Patients in Cohort A, Arm II receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI scans throughout the trial.
Group III: Cohort A, Arm I (nivolumab)Active Control6 Interventions
Patients in Cohort A, Arm I receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI scans throughout the trial.
Group IV: Cohort B, Arm III (nivolumab)Active Control6 Interventions
Patients in Cohort B, Arm III receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI scans throughout the trial.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Illinois CancerCare - WashingtonWashington, IL
Prisma Health Cancer Institute - GreerGreer, SC
University of Michigan Health - Sparrow LansingLansing, MI
Lehigh Valley Hospital-Cedar CrestAllentown, PA
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. [2022]There have been no major advances for the treatment of metastatic urothelial bladder cancer (UBC) in the last 30 years. Chemotherapy is still the standard of care. Patient outcomes, especially for those in whom chemotherapy is not effective or is poorly tolerated, remain poor. One hallmark of UBC is the presence of high rates of somatic mutations. These alterations may enhance the ability of the host immune system to recognize tumour cells as foreign owing to an increased number of antigens. However, these cancers may also elude immune surveillance and eradication through the expression of programmed death-ligand 1 (PD-L1; also called CD274 or B7-H1) in the tumour microenvironment. Therefore, we examined the anti-PD-L1 antibody MPDL3280A, a systemic cancer immunotherapy, for the treatment of metastatic UBC. MPDL3280A is a high-affinity engineered human anti-PD-L1 monoclonal immunoglobulin-G1 antibody that inhibits the interaction of PD-L1 with PD-1 (PDCD1) and B7.1 (CD80). Because PD-L1 is expressed on activated T cells, MPDL3280A was engineered with a modification in the Fc domain that eliminates antibody-dependent cellular cytotoxicity at clinically relevant doses to prevent the depletion of T cells expressing PD-L1. Here we show that MPDL3280A has noteworthy activity in metastatic UBC. Responses were often rapid, with many occurring at the time of the first response assessment (6 weeks) and nearly all were ongoing at the data cutoff. This phase I expansion study, with an adaptive design that allowed for biomarker-positive enriched cohorts, demonstrated that tumours expressing PD-L1-positive tumour-infiltrating immune cells had particularly high response rates. Moreover, owing to the favourable toxicity profile, including a lack of renal toxicity, patients with UBC, who are often older and have a higher incidence of renal impairment, may be better able to tolerate MPDL3280A versus chemotherapy. These results suggest that MPDL3280A may have an important role in treating UBC-the drug received breakthrough designation status by the US Food and Drug Administration (FDA) in June 2014.
Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor. [2021]Bacillus Calmette-Guerin (BCG) is the standard of care for intravesical therapy for carcinoma in situ and non-muscle invasive, nonmetastatic human urothelial carcinoma. Although the responsiveness to this immunotherapeutic is believed to be linked with (i) a high number of somatic mutations and (ii) a large number of tumor-infiltrating lymphocytes, recent findings of the roles that inhibitory immune receptors and their ligands play in tumor evasion may provide insights into the limitations of the effectiveness of BCG and offer new targets for immune-based therapy. In this study, an aggressive, bioluminescent orthotopic bladder cancer model, MB49 tumor cells transfected with luciferase (MB49(luc)), was used to study the antitumor effects of avelumab, an antibody to PD-L1. MB49(luc) murine tumor cells form multifocal tumors on the mucosal wall of the bladder reminiscent of non-muscle invasive, nonmetastatic urothelial carcinomas. MB49(luc) bladder tumors are highly positive for the expression of PD-L1, and avelumab administration induced significant (P
Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. [2022]To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC).
Nivolumab for the treatment of bladder cancer. [2021]The checkpoint inhibitor nivolumab has recently demonstrated effectiveness against metatstatic urothelial carcinoma. Nivolumab is a fully human monoclonal antibody blocking PD-1 and thereby enhancing antitumour immune mechanisms. Areas covered: In this review, the authors describe the treatment of metastatic bladder cancer with nivolumab against the background of the standard treatment with cisplatin-based chemotherapy which can prolong overall survival from 3-6 months in untreated cases to over one year. Different combinations of cisplatin-based chemotherapy can further prolong survival by only a few months. The authors highlight that cancer immunotherapy by checkpoint inhibition offers potential to further prolong patient survival with limited and well manageable toxicity although serious immune-related adverse events may occur. Expert opinion: The response rate to nivolumab and other checkpoint inhibitors after first line chemotherapy remains under 30%. Patients unfit for cisplatin may benefit from first-line cancer immunotherapy. It is unclear which patients will respond and PD-1/PD-L1 expression alone is not a sufficiently reliable response marker. Treatment costs are extreme and further trials will have to clarify which subset of patients in which context of management will have a substantial benefit.
Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy. [2020]Urothelial bladder cancer (UBC) is one of the most common lethal cancer worldwide and the 5-year survival rate has not improved significantly with current treatment protocols during the last decade. Intravesical immunotherapy with Bacillus Calmette-Guérin is currently the standard care for non-muscle invasive UBC. Recently, a subset of patients with locally advanced or metastatic UBC have responded to checkpoint blockade immunotherapy against the programmed cell death 1 protein (PD-1) or its ligand (PD-L1) or the cytotoxic T-lymphocyte antigen 4 that releases the inhibition of T cells, the remarkable clinical efficacy on UBC has brought total five checkpoint inhibitors approved by the FDA in the last 2 years, and this is revolutionizing treatment of advanced UBC. We discuss the rationale for immunotherapy in bladder cancer, progress with blocking the PD-1/PD-L1 pathway for UBC treatment, and ongoing clinical trials. We highlight the complexity of the interactions between cancer cells and the immune system, the genomic basis for response to checkpoint blockade immunotherapy, and potential biomarkers for predicting immunotherapeutic response.
Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. [2022]There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients.
Programmed death ligand-1/programmed death-1 inhibition therapy and programmed death ligand-1 expression in urothelial bladder carcinoma. [2020]After two decades of unchanged paradigms, the treatment strategies for advanced urothelial bladder cancer have been revolutionized by emerging programmed death ligand-1 (PD-L1)/programmed death-1 (PD1) inhibition therapy. Increased evidence is demonstrating the efficacy of PD-L1/PD1 inhibition therapy in both second-line and first-line settings. However, the percentage of patients who benefit from anti-PD-L1/anti-PD1 therapy is still low. Many questions have been raised in the development of biomarker-driven approaches for disease classification and patient selection. In this perspective, we discuss PD-L1/PD1 expression in urothelial bladder carcinoma, review approved anti-PD-L1/anti-PD1 agents for bladder cancer treatment and current ongoing studies investigating combination treatment strategies, and explore PD-L1 expression status for the evaluation of bladder cancer immunotherapy.
PD-L1 assessment in urothelial carcinoma: a practical approach. [2023]Five programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of locally advanced or metastatic urothelial carcinoma of the bladder and the upper urinary tract. Due to restrictions by the FDA and EMA first-line treatment with Atezolizumab and Pembrolizumab in platinum-ineligible patients requires immunohistochemical PD-L1 testing. In the second-line setting all drugs are approved without PD-L1 testing. Used PD-L1 assays in clinical trials include the 28-8 pharmDx (Nivolumab), the 22C3 pharmDx (Pembrolizumab), Ventana SP142 (Atezolizumab), and the Ventana PD-L1 SP263 assays (Durvalumab). Differences in antibodies, needed platforms and testing algorithms have raised questions about interchangeability and comparability among these assays and their diagnostic use. We provide a practical review about the current recommendations, used assays and algorithms of PD-L1 testing in urothelial carcinoma to help oncologists, urologists and pathologists to understand analytical features, differences in antibody assays, differences in scoring algorithms and comparability of various PD-L1 assays. We reviewed and summarized published studies from the last four years (2016-2019) on PD-L1 testing in bladder cancer and present a condensed practical guideline including pre-analytical, analytical and test-specific issues.
PD-L1 testing in urothelial bladder cancer: essentials of clinical practice. [2021]While immunotherapy has become an increasingly attractive strategy in patients with urothelial bladder cancer, the need for a biomarker to identify patients whose cancer is the most likely to respond has never been more crucial. This review systematically evaluates evidence regarding PD-L1 as a predictive biomarker of response to anti-PD(L)1 monoclonal antibodies in patients with urothelial bladder carcinoma, and discusses its current limits in routine clinical practice.
A phase I open label dose-escalation study to evaluate the tolerability, safety and immunological efficacy of sub-urothelial durvalumab injection in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer (SUBDUE-1, SUB-urothelial DUrvalumab injection-1 study): clinical trial protocol. [2021]This article presents the clinical trial protocol for a phase I open label dose-escalation study to evaluate the tolerability, safety and immunological efficacy of sub-urothelial durvalumab injection in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer (NMIBC), the SUB-urothelial DUrvalumab injection-1 study (SUBDUE-1). The primary objectives of this study are to assess the safety of sub-urothelial injection of durvalumab using patient reported outcome measures and observed local or systemic adverse events. The secondary objectives are to examine the local immunological efficacy of sub-urothelial administration of durvalumab.
Integrating angiogenesis signature and tumor mutation burden for improved patient stratification in immune checkpoint blockade therapy for muscle-invasive bladder cancer. [2023]Muscle-invasive bladder cancer (MIBC) patients have benefitted greatly from immune checkpoint blockade (ICB) therapy. However, there is a pressing need to identify factors underlying the heterogeneity of clinical responses to ICB.