Blood Test and Immunotherapy for Bladder Cancer

Recruiting at 396 trial locations

Overseen By Joseph W. Kim

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 73

Duration: 48 weeks

1190 Participants Needed

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}

Research Team

Matthew D Galsky

Principal Investigator

Alliance for Clinical Trials in Oncology

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.

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
• Relatlimab

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Five PD-1/PD-L1 inhibitors are approved for treating advanced bladder cancer, but first-line treatments like Atezolizumab and Pembrolizumab require PD-L1 testing for platinum-ineligible patients, while second-line treatments do not.

The review highlights the differences in PD-L1 testing assays and their implications for clinical practice, providing guidelines to help healthcare professionals navigate the complexities of these tests in urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 assessment in urothelial carcinoma: a practical approach. Eckstein, M., Cimadamore, A., Hartmann, A., et al.[2023]

Durvalumab, a monoclonal antibody targeting PD-L1, showed a manageable safety profile in patients with advanced urothelial bladder cancer, with common side effects including fatigue and diarrhea, but no severe (grade 4 or 5) adverse events reported.

The treatment demonstrated a 31% overall response rate, with a significantly higher response of 46.4% in patients with PD-L1-positive tumors, indicating that PD-L1 expression may play a crucial role in the efficacy of durvalumab.

NCBI (Pubmed)

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. Massard, C., Gordon, MS., Sharma, S., et al.[2022]

The introduction of PD-L1/PD-1 inhibition therapy has significantly changed treatment strategies for advanced urothelial bladder cancer, showing efficacy in both first-line and second-line treatment settings.

Despite the promise of PD-L1/PD-1 therapies, the proportion of patients who actually benefit from these treatments remains low, highlighting the need for better biomarker-driven approaches to improve patient selection and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed death ligand-1/programmed death-1 inhibition therapy and programmed death ligand-1 expression in urothelial bladder carcinoma. Yu, WB., Rao, JY.[2020]

In a study of 848 muscle-invasive bladder cancer patients, those who did not respond to PD-L1 blockade therapy were found to have a high angiogenesis signature, indicating a link between this signature and an immunosuppressive tumor environment.

The research identified a specific subgroup of patients resistant to immune checkpoint blockade, characterized by high angiogenesis and low tumor mutation burden, suggesting that combining these factors could help better predict patient responses to therapy.

NCBI (Pubmed)

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. Shao, F., Jin, K., Li, B., et al.[2023]

Intravesical immunotherapy with Bacillus Calmette-Guérin remains the standard treatment for non-muscle invasive urothelial bladder cancer (UBC), but recent advances in checkpoint blockade immunotherapy targeting PD-1 and PD-L1 have shown promise for patients with advanced UBC, leading to the FDA approval of five checkpoint inhibitors in the last two years.

The effectiveness of these immunotherapies highlights the importance of understanding the complex interactions between cancer cells and the immune system, as well as the potential for genomic markers to predict patient responses to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy. Cheng, W., Fu, D., Xu, F., et al.[2020]

Avelumab, an antibody targeting PD-L1, showed significant antitumor effects in a bladder cancer model, indicating its potential as an effective treatment for non-muscle invasive urothelial carcinoma.

The study found that the antitumor effects of avelumab were more reliant on CD4 T cells rather than CD8 T cells, suggesting that enhancing the adaptive immune response could improve treatment outcomes for bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor. Vandeveer, AJ., Fallon, JK., Tighe, R., et al.[2021]

PD-L1 expression is being evaluated as a predictive biomarker for the effectiveness of anti-PD(L)1 monoclonal antibodies in treating advanced or metastatic urothelial bladder cancer, highlighting its potential role in personalizing immunotherapy.

Currently, only patients with PD-L1 positive status are eligible for first-line treatment with atezolizumab and pembrolizumab, but the effectiveness of these therapies in other settings does not rely on PD-L1 status, indicating a need for further research into additional biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 testing in urothelial bladder cancer: essentials of clinical practice. Rouanne, M., Radulescu, C., Adam, J., et al.[2021]

Nivolumab, a PD-1 blocking monoclonal antibody, shows effectiveness in treating metastatic urothelial carcinoma, potentially offering better survival rates compared to traditional cisplatin-based chemotherapy, which typically extends survival by only a few months.

While nivolumab has manageable toxicity, its response rate after first-line chemotherapy is under 30%, and further research is needed to identify which patients will benefit most from this treatment, especially given the high costs involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for the treatment of bladder cancer. Hakenberg, OW.[2021]

References

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

PD-L1 assessment in urothelial carcinoma: a practical approach. [2023]

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]

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]

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]

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

Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy. [2020]

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]

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

PD-L1 testing in urothelial bladder cancer: essentials of clinical practice. [2021]

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

Nivolumab for the treatment of bladder cancer. [2021]