Autogene Cevumeran + Nivolumab for Bladder Cancer

(IMCODE004 Trial)

Recruiting at 34 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for high-risk bladder cancer. Researchers aim to determine if adding autogene cevumeran (an experimental treatment) to nivolumab is more effective than nivolumab alone. Nivolumab already aids the immune system in fighting cancer. People who have undergone surgery for muscle-invasive bladder cancer but have no remaining disease might be suitable candidates. The trial seeks to discover if the new combination can prevent cancer recurrence. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that the combination of autogene cevumeran and nivolumab is being tested for safety in people with high-risk bladder cancer. Other studies have used nivolumab safely to treat various types of cancer. Most patients tolerate it well, though some have experienced side effects like tiredness, skin rash, or nausea.

Autogene cevumeran is a newer treatment and remains under study. Since this trial is in an early stage, limited safety information is available. However, this phase is designed to closely monitor and ensure the treatment's safety for participants. This process helps determine how well patients can tolerate the new combination of treatments. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for bladder cancer?

Unlike the standard treatments for bladder cancer, which often include chemotherapy and immunotherapies like nivolumab alone, Autogene Cevumeran is an mRNA-based cancer vaccine that works alongside nivolumab. Researchers are excited about this combination because Autogene Cevumeran is designed to train the immune system to specifically target cancer cells, potentially enhancing the effectiveness of nivolumab. This dual approach could lead to more personalized and powerful treatment options, potentially improving outcomes for patients compared to existing therapies.

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

Studies have shown that nivolumab, a type of immunotherapy, can help treat bladder cancer by enabling the body's immune system to find and attack cancer cells. In this trial, participants will receive either nivolumab with autogene cevumeran or nivolumab with a saline solution. Autogene cevumeran is a personalized vaccine designed to teach the immune system to target specific cancer proteins. Early research suggests that combining autogene cevumeran with nivolumab might improve treatment outcomes, potentially enhancing the immune system's ability to fight cancer cells. Although more research is needed, these treatments are promising because they specifically target cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06534983

NCT06534983 | A Study to Evaluate the Efficacy and ... The main purpose of the study is to evaluate the efficacy of adjuvant treatment with autogene cevumeran plus nivolumab compared with nivolumab in participants ...

2. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/bladder-cancer/a-study-to-evaluate-the-efficacy-and-safety-of-autogene-25008.html

Clinical trial for Muscle Invasive Urothelial Carcinoma -... The main purpose of the study is to evaluate the efficacy of adjuvant treatment with autogene cevumeran plus nivolumab compared with nivolumab in participants ...

3. bcan.org bcan.org/clinicaltrials/autogene-cevumeran-with-nivolumab-versus-nivolumab-alone-in-participants-with-high-risk-muscle-invasive-urothelial-carcinoma-miuc/

Autogene Cevumeran With Nivolumab Versus ... The main purpose of the study is to evaluate the efficacy of adjuvant treatment with autogene cevumeran plus nivolumab compared with nivolumab in participants ...

4. blog.providence.org blog.providence.org/regional-blog-news/personalized-mrna-vaccine-and-next-gen-immunotherapy-two-new-cancer-trials-at-providence

Personalized mRNA vaccine and next-gen immunotherapy The combination of autogene cevumeran and nivolumab could improve the results of chemotherapy plus surgery, or potentially could be a new ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-08517

A Study to Evaluate the Efficacy and Safety of Autogene ... The main purpose of the study is to evaluate the efficacy of adjuvant treatment with autogene cevumeran plus nivolumab compared with nivolumab in participants ...