Immune Checkpoint Therapy Duration for Bladder Cancer

(IMAGINE Trial)

Not currently recruiting at 403 trial locations

Overseen By Xiao X. Wei, MD, MAS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: PD-1/L1 inhibitors

Must not be taking: Immunosuppressants

Disqualifiers: Tuberculosis, Active hepatitis, Uncontrolled HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 4

Duration: Approximately 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether people with urothelial cancer (a type of bladder cancer) can stop immunotherapy early and still maintain the same survival rates as those who continue. Researchers aim to determine if stopping treatment after about a year can still shrink the tumor while reducing side effects, improving mental health, and lowering costs. The trial involves treatments with monoclonal antibodies like atezolizumab (Tecentriq) and pembrolizumab (KEYTRUDA), which help the immune system fight cancer. This trial might suit someone who has been on one of these treatments for 12-15 months, with stable or improved cancer, and no severe side effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on immunosuppressive medication exceeding 10 mg/day of prednisone or its equivalent.

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

Research has shown that treatments like nivolumab, used in immune checkpoint therapy for bladder cancer, have generally been well-tolerated by patients in past studies. Common side effects include fatigue, muscle aches, nausea, and reduced appetite. More serious side effects, such as lung disease or pneumonia, have been reported but occur in only a small percentage of patients.

The FDA has already approved nivolumab for treating urinary tract cancers, indicating a certain level of confidence in its safety for this type of cancer. This approval provides extra reassurance about its use in these treatments.

For the other treatments in this trial—atezolizumab, avelumab, durvalumab, and pembrolizumab—similar drugs have demonstrated similar safety profiles in past research. Generally, stopping these treatments early may reduce side effects, improve mental health, and lower costs without affecting patient survival. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about immune checkpoint inhibitors like atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab because they offer a novel approach to treating bladder cancer by harnessing the body's immune system to fight cancer cells. Unlike traditional chemotherapy, which directly targets and kills cancer cells, these treatments work by blocking proteins that prevent the immune system from attacking tumors. This can potentially lead to more durable and long-lasting responses. Moreover, the ability to discontinue and then restart treatment at signs of disease progression adds a flexible dynamic not typical of conventional therapies, offering hope for improved management of the condition.

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

Research shows that drugs called immune checkpoint inhibitors, such as nivolumab, can effectively treat urothelial cancer. In this trial, participants in Arm A will continue receiving immune checkpoint inhibitors like nivolumab, while those in Arm B will discontinue treatment. One study found that patients with upper tract urothelial carcinoma who took nivolumab had a 73.1% chance of remaining cancer-free and an 85.1% chance of overall survival after two years. This indicates that nivolumab can significantly reduce the risk of cancer recurrence. Additionally, those treated with nivolumab had a 30% lower chance of cancer returning compared to those who received a placebo. These results suggest that immune checkpoint inhibitors might enhance the body's ability to fight and control bladder cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Xiao X. Wei, MD, MAS

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with urothelial carcinoma, a type of bladder cancer. Participants must have had at least one cycle of FDA-approved immune therapy and not show disease progression after 12-15 months of treatment. They can't join if they're pregnant, breastfeeding, unwilling to use birth control, or have certain infections or a history of other cancers.

Inclusion Criteria

My cancer is in the bladder, renal pelvis, ureter, urethra, or prostate.

My cancer is advanced but has not been treated with immune therapy yet.

I have undergone at least one treatment cycle with an FDA-approved immunotherapy for my advanced or metastatic bladder cancer.

Exclusion Criteria

No history of allogeneic organ transplantation

I have an autoimmune or inflammatory disorder but don't need more than 10 mg/day of prednisone.

I don't have tuberculosis, hepatitis B or C, or uncontrolled HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immune checkpoint inhibitors such as pembrolizumab, nivolumab, atezolizumab, durvalumab, or avelumab. Treatment cycles repeat every 21 to 42 days depending on the specific drug regimen.

Approximately 1 year

Follow-up

Participants are monitored for overall survival, progression-free survival, and adverse events after treatment completion.

5 years

Follow-up at 4 weeks, then every 6 months

Treatment-free Interval (Arm B)

Participants in Arm B discontinue ICI treatment and may restart upon disease progression at physician discretion.

Varies based on disease progression

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Avelumab
• Durvalumab
• Nivolumab
• Pembrolizumab

Trial Overview

The study compares the effects of stopping immune checkpoint inhibitors (avelumab, durvalumab, pembrolizumab, nivolumab, atezolizumab) after about a year versus continuing them. It aims to see if early discontinuation affects survival rates while reducing side effects and costs.

How Is the Trial Designed?

Group I: Arm B (immune checkpoint inhibitor) Experimental Treatment 5 Interventions

DISCONTINUATION OF ICI TREATMENT: Patients receiving ICI treatment will discontinue ICI treatment within 1 cycle length after randomization. Cycle length is determined by the ICI regimen the patient is receiving at randomization. At disease progression patients may restart the same ICI treatment they were receiving upon randomization at physician discretion.

Group II: Arm A (immune checkpoint inhibitor) Active Control 5 Interventions

CONTINUATION OF ICI TREATMENT: Patients receive either pembrolizumab intravenously (IV) over 30 minutes on day 1, nivolumab IV over 30 minutes on days 1 and 15, atezolizumab IV over 30-60 minutes on day 1, durvalumab IV over 60 minutes on days 1 and 15, or avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 21 or 42 days for pembrolizumab, every 21 days for atezolizumab, and 28 days for nivolumab, durvalumab, and avelumab in the absence of disease progression or unacceptable toxicity.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 1 study involving 8 patients with localized muscle invasive bladder cancer, the combination of atezolizumab, radiation therapy, and gemcitabine resulted in significant gastrointestinal toxicity, leading to dose adjustments and the study's termination.

Despite the serious side effects observed, no grade 4 or 5 adverse effects were reported, indicating that while the treatment combination is concerning in terms of safety, it did not lead to the most severe complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Trial of Atezolizumab Plus Trimodal Therapy in Patients With Localized Muscle-Invasive Bladder Cancer. Marcq, G., Souhami, L., Cury, FL., et al.[2021]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

In a phase 3 study involving 487 patients with advanced urothelial carcinoma, the combination of pembrolizumab and lenvatinib did not show improved progression-free survival (4.5 months) or overall survival (11.8 months) compared to pembrolizumab with placebo.

The combination treatment resulted in a higher rate of severe adverse events (51%) compared to the placebo group (27%), leading to the conclusion that the benefit-to-risk ratio was not favorable for using lenvatinib with pembrolizumab as first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Matsubara, N., de Wit, R., Balar, AV., et al.[2023]

Atezolizumab, an anti-PD-L1 therapy, showed long-term safety and efficacy in patients with metastatic urothelial carcinoma, with a median follow-up of 37.8 months and a low incidence of severe treatment-related adverse events (9%).

The treatment resulted in a 26% objective response rate, with a median duration of response of 22.1 months, and median overall survival of 10.1 months, particularly benefiting patients with higher PD-L1 expression on immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. Petrylak, DP., Powles, T., Bellmunt, J., et al.[2022]

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

Atezolizumab, an anti-PD-L1 monoclonal antibody, has shown durable responses in treating locally advanced and metastatic urothelial cancer, especially in patients who have failed platinum-based chemotherapy or are ineligible for cisplatin.

The treatment with atezolizumab has a more favorable toxicity profile compared to traditional cytotoxic chemotherapy, making it a promising option for patients with advanced bladder cancer, although further research is needed to identify additional predictive markers for response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. Crist, M., Balar, A.[2019]

Citations

1.

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. •.

2.

opdivohcp.com

opdivohcp.com/efficacy/uc

Efficacy Data for Urothelial Carcinoma (UC) - Opdivo

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and ...

3.

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.

4.

ascopubs.org

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

Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk ...

Adjuvant NIVO demonstrated statistically significant and clinically meaningful disease-free survival (DFS) benefit vs PBO in pts with high-risk MIUC after ...

5.

opdivo.com

opdivo.com/bladder-urinary-tract-cancer/clinical-trial-results/after-surgery-immunotherapy

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.

opdivohcp.com

opdivohcp.com/safety/uc

Safety Profile for Urothelial Carcinoma (UC) - Opdivo

The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock ...

7.

opdivo.com

opdivo.com/bladder-urinary-tract-cancer/clinical-trial-results/advanced-previously-treated-immunotherapy

Previously Treated Advanced Bladder or Urinary Tract ...

7 out of 270 people, or 3%, saw tumors disappear completely in response to OPDIVO® for previously treated advanced bladder cancer.

8.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/nivolumab-treatment-urothelial-carcinoma

Nivolumab for Treatment of Urothelial Carcinoma

The most common adverse reactions (reported in at least 20% of patients) were fatigue, musculoskeletal pain, nausea, and decreased appetite.

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8166422/

Nivolumab in Patients with Advanced Platinum-Resistant ...

We report efficacy and safety with extended follow-up, and exploratory biomarker analyses from the phase II CheckMate 275 trial to identify biomarkers of ...

10.

opdivo.com

opdivo.com/bladder-urinary-tract-cancer

Bladder or Urinary Tract (Urothelial) Cancer Treatment

OPDIVO® (nivolumab) is an FDA-approved immunotherapy that can be used alone, or with chemotherapy, to treat three different types of urinary tract cancer ...