Blood Test and Immunotherapy for Bladder Cancer

Recruiting at 492 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

992 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether a blood test can identify bladder cancer patients at risk of recurrence after surgery, who might benefit from additional treatment called immunotherapy. It examines circulating tumor DNA (ctDNA), which is cancer DNA found in the blood, to determine if cancer remains after surgery. Patients will receive immunotherapy drugs like nivolumab (Opdivo) and, in some cases, a combination with relatlimab (Opdualag) to assess if it prolongs life or delays cancer progression. Those who have undergone surgery for bladder, kidney, ureter, or urethra cancer due to urothelial cancer, have no visible cancer left, but are at high risk for recurrence, may be suitable for this trial. As a Phase 2, Phase 3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking cancer treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that nivolumab is generally well-tolerated by people with bladder and urinary tract cancers. One study found that patients treated with nivolumab had a 30% lower chance of cancer recurrence after surgery compared to those who received a placebo. This finding suggests that nivolumab can be an effective and safe option for many patients. Another study demonstrated that patients using nivolumab had a 24% lower risk of death, further supporting its safety and effectiveness.

For the combination of nivolumab and relatlimab, available data suggest that adding relatlimab does not increase safety concerns. In studies with advanced-stage lung cancer, patients did not experience more severe side effects with this combination. This implies that the combination is manageable in terms of side effects, even when used with other treatments like chemotherapy.

Overall, both nivolumab alone and the combination with relatlimab appear safe, with side effects that are usually manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they harness the power of immunotherapy, offering a different approach compared to traditional chemotherapy. Nivolumab is a type of immune checkpoint inhibitor that helps the body's immune system recognize and attack cancer cells more effectively. Relatlimab works by targeting another checkpoint, potentially enhancing the immune response further when used alongside nivolumab. Additionally, the use of ctDNA surveillance in one of the treatment arms allows for personalized monitoring of cancer progression, which could lead to more tailored and timely treatment interventions. These features combine to create a promising strategy that may improve outcomes for patients with bladder cancer.

What evidence suggests that this trial's treatments could be effective for urothelial cancer?

Research has shown that nivolumab, which participants in this trial may receive, can help lower the risk of bladder cancer returning after surgery. One study found that people who took nivolumab had a 30% lower chance of their cancer returning compared to those who took a placebo. Another study reported that after 24 months, 73.1% of patients were free of cancer, and 85.1% were still alive. In this trial, some participants will receive a combination of nivolumab and relatlimab, which helps the immune system better recognize and attack cancer cells. This combination has shown promise in stopping the disease from worsening. ^{3 6 7 8 9}

Who Is on the Research Team?

Matthew D Galsky

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI and may undergo cystoscopy 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 and may undergo cystoscopy 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 and may undergo cystoscopy throughout the trial.

Group IV: Cohort B, Arm III (nivolumab) Active Control 5 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 and may undergo cystoscopy throughout the trial.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12150186/

Clinical Outcomes in Patients With Muscle-Invasive Urothelial ... This cohort study examines treatment patterns and clinical outcomes for patients with muscle-invasive urothelial carcinoma treated with adjuvant nivolumab.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1078143925002662

Efficacy of adjuvant nivolumab in patients with upper tract ... 24-month disease-free survival (DFS) reached 73.1%, and overall survival (OS) to 85.1% in upper tract urothelial carcinoma (UTUC) group.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.658

Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk ... Background: In the phase 3, randomized, double-blind CheckMate 274 trial, adjuvant NIVO demonstrated statistically significant and clinically ...

4. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-bladder-cancer/164022-esmo-2025-adjuvant-nivolumab-versus-placebo-for-high-risk-muscle-invasive-urothelial-carcinoma-5-year-efficacy-and-ctdna-results-from-checkmate-274.html

ESMO 2025: Adjuvant Nivolumab versus Placebo for High- ... ESMO 2025 5-year efficacy and ctDNA results from CheckMate 274, adjuvant nivolumab versus placebo for high-risk muscle invasive urothelial carcinoma.

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Clinical trial results for bladder or urinary tract cancer after ... People given OPDIVO had a 30% lower risk of their cancer returning after surgery than those given placebo.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601741/

Clinical Review - Nivolumab (Opdivo) - NCBI Bookshelf - NIH The 5-year survival among patients with localized muscle-invasive urothelial carcinoma (MIUC) is approximately 40% to 50%.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00340

Adjuvant Nivolumab in High-Risk Muscle-Invasive ... The current OS data show a 24% reduction in the risk of death for patients treated with nivolumab in the ITT population and a 44% reduction for ...

8. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-bladder-cancer/158278-asco-gu-2025-adjuvant-nivolumab-vs-placebo-for-high-risk-muscle-invasive-urothelial-carcinoma-additional-efficacy-outcomes-including-overall-survival-in-patients-with-mibc-from-checkmate-274.html

ASCO GU 2025: Adjuvant Nivolumab vs Placebo for High- ... The primary endpoints were disease free survival in ITT and tumor PD-L1 expression ≥ 1% patients. Overall survival in ITT and PD-L1 ≥ 1% ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa2034442

Adjuvant Nivolumab versus Placebo in Muscle-Invasive ... On the basis of CheckMate 274 results, nivolumab improved clinical outcomes when administered as adjuvant therapy to patients with urothelial ...