Blood Test and Immunotherapy for Bladder Cancer

Recruiting in Palo Alto (17 mi)

+368 other locations

Overseen by Matthew D Galsky

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: National Cancer Institute (NCI)

Must be taking: Immunotherapy

Must not be taking: PD-1/PD-L1, LAG-3

Disqualifiers: Autoimmune disease, Hepatitis, Myocarditis, others

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 the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any immunosuppressive agents or systemic corticosteroids above a certain dose within 14 days before joining the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Nivolumab, Opdivo, Relatlimab, Opdualag, BMS-986016, relatlimab-rmbw for bladder cancer?

Research shows that drugs targeting the PD-1/PD-L1 pathway, like Nivolumab and similar treatments, have been effective in treating advanced bladder cancer. These drugs help the immune system attack cancer cells, and several have been approved for use in bladder cancer, indicating their potential effectiveness. ^{1 2 3 4 5}

How does the immunotherapy treatment for bladder cancer differ from other treatments?

This treatment is unique because it uses immunotherapy drugs like Durvalumab and Avelumab, which are antibodies that target PD-L1, a protein that helps cancer cells hide from the immune system. Unlike traditional chemotherapy, these drugs enhance the body's immune response to fight cancer, offering a different approach with potentially fewer side effects. ^{1 2 6 7 8}

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 had a complete bladder removal and lymph node surgery 3 to 12 weeks ago.

I have moderate heart failure.

I can walk and take care of myself but cannot do any physical work.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive nivolumab and/or relatlimab intravenously every 28 days for up to 12 cycles

48 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Visits at weeks 60, 72, 84, 96, 120, 144, 196, and 248

Treatment Details

Interventions

• Nivolumab (Immunotherapy)
• Relatlimab (Immunotherapy)

Trial Overview 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.

Participant Groups

Group I: Cohort B, Arm IV (ctDNA surveillance, nivolumab) Experimental Treatment 7 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 Treatment 7 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 Control 6 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 Control 6 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 Nearby Select from list below to view details:

Illinois CancerCare - Washington Washington, IL

Prisma Health Cancer Institute - Greer Greer, SC

University of Michigan Health - Sparrow Lansing Lansing, MI

Lehigh Valley Hospital-Cedar Crest Allentown, PA

More Trial Locations

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. China pubmed.ncbi.nlm.nih.gov

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.

2. United States pubmed.ncbi.nlm.nih.gov

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).

3. United States pubmed.ncbi.nlm.nih.gov

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.

4. United States pubmed.ncbi.nlm.nih.gov

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.

5. United States pubmed.ncbi.nlm.nih.gov

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.

6. United States pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

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.

8. England pubmed.ncbi.nlm.nih.gov

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.