Autogene Cevumeran + Nivolumab for Bladder Cancer

(IMCODE004 Trial)

Recruiting at 97 trial locations

Overseen By Reference Study ID Number: BO45230 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must be taking: Nivolumab

Must not be taking: Chemotherapy, Hormonal therapy

Disqualifiers: Partial cystectomy, Other malignancies, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 12 months

362 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop any approved anti-cancer therapy, including chemotherapy or hormonal therapy, at least 3 weeks before starting the study treatment.

What evidence supports the effectiveness of the drug Nivolumab for bladder cancer?

Nivolumab, a drug that helps the immune system fight cancer, has shown promise in treating bladder cancer, especially for patients whose cancer has returned after chemotherapy. Studies have found that it can prolong the time patients live without the disease getting worse. ^{1 2 3 4 5}

Is the combination of Autogene Cevumeran and Nivolumab safe for humans?

Nivolumab, a part of the treatment, is generally well tolerated in bladder cancer patients, with common side effects including tiredness, low white blood cell count, anemia, muscle pain, decreased appetite, and nausea. However, there have been reports of non-bacterial bladder inflammation as a side effect of similar immunotherapies. ^{2 6 7 8 9}

What makes the drug Nivolumab unique for treating bladder cancer?

Nivolumab is unique for treating bladder cancer because it is an immune checkpoint inhibitor that targets the PD-1 pathway, helping the immune system attack cancer cells. It is used as a second-line treatment for patients whose cancer has progressed after platinum-based chemotherapy, offering a new option for those who cannot tolerate traditional chemotherapy. ^{1 2 3 10 11}

What is the purpose of this trial?

The main purpose of the study is to evaluate the efficacy of adjuvant treatment with autogene cevumeran plus nivolumab compared with nivolumab in participants with high risk MIUC. In this study participants will be enrolled in a safety run-in phase to receive autogene cevumeran + nivolumab. This phase will be conducted to monitor and ensure the safety of study participants. After all participants in the safety run-in have been enrolled to receive autogene cevumeran + nivolumab, further participants will be randomization in either autogene cevumeran + nivolumab or the saline + nivolumab arm.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with high-risk muscle-invasive urothelial carcinoma who've had surgery but no prior chemo. They must be fully recovered from surgery, have good performance status, and can't have HIV or active hepatitis B. Participants need to provide tumor tissue and not show any signs of disease spread on recent scans.

Inclusion Criteria

I have fully recovered from bladder or kidney removal surgery within the last 4 months.

I have tested negative for HIV.

My cancer was classified as stage T3-4 or N+ but has not spread to distant organs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Participants receive autogene cevumeran + nivolumab to monitor and ensure safety

4 weeks

1 visit (in-person)

Treatment

Participants are randomized to receive either autogene cevumeran + nivolumab or saline + nivolumab

12 months

12 visits (in-person, once every 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

Treatment Details

Interventions

• Autogene Cevumeran
• Nivolumab

Trial Overview The study tests the effectiveness of Autogene Cevumeran combined with Nivolumab versus Nivolumab alone in patients after bladder cancer surgery. Initially, all participants receive both drugs to ensure safety before being randomly assigned to either continue this combination or switch to Nivolumab with saline.

Participant Groups

Group I: Autogene Cevumeran + Nivolumab Experimental Treatment 2 Interventions

Participants will receive autogene cevumeran along with nivolumab intravenously (IV) at a recommended dose at specified timepoints.

Group II: Saline+Nivolumab Active Control 2 Interventions

Participants will receive saline solution along with 480 milligrams (mg) of nivolumab, IV, once every 4 weeks (Q4W) for 1 year.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

BioNTech SE

Industry Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Findings from Research

In a phase 2 study involving 270 patients with metastatic urothelial carcinoma, nivolumab demonstrated a confirmed objective response rate of 19.6%, indicating it can provide meaningful clinical benefits even after previous treatments have failed.

The treatment was generally well-tolerated, with 18% of patients experiencing grade 3-4 adverse events, primarily fatigue and diarrhea, and only three treatment-related deaths, suggesting an acceptable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Sharma, P., Retz, M., Siefker-Radtke, A., et al.[2022]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

Recent advancements in immunotherapy, particularly immune-checkpoint inhibitors like atezolizumab and pembrolizumab, have shown significant anti-tumor activity and improved survival rates in patients with advanced urothelial carcinoma who have previously failed platinum-based chemotherapy.

These immune-checkpoint inhibitors have tolerable safety profiles and have been FDA-approved for use in bladder cancer, marking a shift in treatment standards and offering hope for better long-term outcomes compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Urothelial Cancer: Recent Results and Future Perspectives. Farina, MS., Lundgren, KT., Bellmunt, J.[2022]

In a study involving 709 patients with muscle-invasive urothelial carcinoma, nivolumab did not lead to any clinically meaningful deterioration in health-related quality of life (HRQoL) compared to placebo, indicating it is a safe treatment option.

Nivolumab was found to maintain HRQoL while also prolonging the time until cancer recurrence, demonstrating its efficacy in improving patient outcomes after radical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life with Adjuvant Nivolumab After Radical Resection for High-risk Muscle-invasive Urothelial Carcinoma: Results from the Phase 3 CheckMate 274 Trial. Witjes, JA., Galsky, MD., Gschwend, JE., et al.[2023]

Recent advancements in the treatment of advanced-stage urothelial carcinoma, a common type of bladder cancer, include the FDA approval of several immune checkpoint inhibitors such as nivolumab, pembrolizumab, and atezolizumab.

Despite these promising new therapies, clinicians face challenges in selecting the most effective treatment options for patients, particularly in determining the best first-line or second-line therapies to improve overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Changing Treatment Landscape for Metastatic Urothelial Carcinoma. Flaig, TW.[2019]

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]

A 48-year-old male with intrahepatic cholangiocarcinoma developed non-bacterial cystitis as an immune-related adverse event after treatment with PD-1 and PD-L1 antibodies, specifically nivolumab and atezolizumab.

Despite multiple urine cultures showing no bacteria, the patient experienced urinary tract discomfort and bladder inflammation, highlighting the potential for immunotherapy to cause non-infectious inflammatory responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Report of Non-Bacterial Cystitis Caused by Immune Checkpoint Inhibitors. Zhu, S., Bian, L., Lv, J., et al.[2022]

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 retrospective study of 31 patients with locally advanced or metastatic bladder cancer, the combination of tislelizumab and chemotherapy (TGC) showed a median progression-free survival (PFS) of 36 weeks, significantly better than the 29 weeks observed with chemotherapy alone (GC).

While TGC treatment resulted in a higher incidence of grade ≥3 treatment-related adverse events (35.7% vs 23.5% for GC), this increase was not statistically significant, indicating that TGC is generally well tolerated while providing promising antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab in combination with gemcitabine plus cisplatin chemotherapy as first-line adjuvant treatment for locally advanced or metastatic bladder cancer: a retrospective study. Ren, X., Tian, Y., Wang, Z., et al.[2022]

Nivolumab, a monoclonal antibody that blocks PD-1, shows a 20% overall response rate in patients with metastatic urothelial carcinoma after failing first-line platinum-based chemotherapy, indicating its potential as a treatment option.

While nivolumab is associated with manageable toxicity, serious immune-related adverse events can occur, and current biomarkers like PD-1/PD-L1 expression are not reliable for predicting patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and its use in the second-line treatment of metastatic urothelial cancer. Raggi, D., Necchi, A., Giannatempo, P.[2019]

Pembrolizumab significantly improves survival and quality of life for patients with advanced urothelial cancer who cannot tolerate cisplatin-based chemotherapy, offering an increase of approximately 2.11 to 2.16 years in overall survival and 1.71 to 1.75 quality-adjusted life years (QALYs) compared to standard treatments like carboplatin plus gemcitabine and gemcitabine monotherapy.

Despite being associated with higher costs (an increase of €90,520 compared to carboplatin plus gemcitabine), pembrolizumab is considered cost-effective at a threshold of €100,000/QALY, making it a viable first-line treatment option for this patient population in Sweden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. Patterson, K., Prabhu, V., Xu, R., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. [2022]

2. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Immunotherapy in Urothelial Cancer: Recent Results and Future Perspectives. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life with Adjuvant Nivolumab After Radical Resection for High-risk Muscle-invasive Urothelial Carcinoma: Results from the Phase 3 CheckMate 274 Trial. [2023]

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

The Changing Treatment Landscape for Metastatic Urothelial Carcinoma. [2019]

6. Switzerland 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. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Case Report of Non-Bacterial Cystitis Caused by Immune Checkpoint Inhibitors. [2022]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Tislelizumab in combination with gemcitabine plus cisplatin chemotherapy as first-line adjuvant treatment for locally advanced or metastatic bladder cancer: a retrospective study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Nivolumab and its use in the second-line treatment of metastatic urothelial cancer. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. [2022]