Immunotherapy for Bladder Cancer

Recruiting at 112 trial locations

Overseen By Reference Study ID Number: BO44157 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Antibiotics, Antivirals, Immunosuppressants, others

Disqualifiers: Pregnancy, CNS metastases, Autoimmune disease, 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: 4

Duration: 12 weeks

204 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are currently on certain treatments like anti-cancer therapy, systemic immunosuppressive medication, or antiviral therapy for hepatitis B. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab for bladder cancer?

Atezolizumab has shown effectiveness in treating advanced bladder cancer, with a 15% response rate and 36% one-year survival in patients who had previously received chemotherapy, and a 24% response rate and 57% one-year survival in those who had not. It is FDA approved for use in these cases, indicating better outcomes compared to other second-line treatments. ^{1 2 3 4 5}

Is atezolizumab safe for treating bladder cancer?

Atezolizumab has shown a favorable safety profile in clinical trials for advanced bladder cancer, with most treatment-related side effects being manageable. Serious side effects occurred in a small percentage of patients. ^{1 2 3 5 6}

What makes the drug Atezolizumab unique for treating bladder cancer?

Atezolizumab is unique because it is an immunotherapy drug that blocks the PD-L1 protein, helping the immune system attack bladder cancer cells more effectively. It is approved for use when other treatments, like chemotherapy, have failed, and it has shown better response rates and survival outcomes compared to traditional second-line treatments. ^{1 2 3 4 7}

What is the purpose of this trial?

This study will evaluate the safety of tobemstomig alone or in combination with tiragolumab compared with atezolizumab in participants with previously untreated, locally advanced or metastatic urothelial cancer (mUC) who are ineligible to receive a platinum containing chemotherapy.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-LaRoche

Eligibility Criteria

This trial is for adults with advanced bladder cancer who haven't had treatment yet and can't have platinum chemotherapy. They should be relatively active (ECOG ≤ 2), not pregnant, without serious heart or kidney issues, no recent major surgeries, and free from certain infections like hepatitis B/C and tuberculosis.

Inclusion Criteria

My blood and organs are functioning well.

Negative for hepatitis B and hepatitis C virus (HCV)

My heart is healthy and functions well.

Exclusion Criteria

I have high calcium levels in my blood that are causing symptoms.

History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

I have had lung conditions like pulmonary fibrosis or pneumonitis, or my CT scan shows active pneumonitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tobemstomig alone, tobemstomig with tiragolumab, or atezolizumab every 3 weeks

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab
• RO7247669
• Tiragolumab

Trial Overview The study tests the effectiveness of Tobemstomig alone or with Tiragolumab versus Atezolizumab in untreated metastatic urothelial cancer patients. It aims to see which combination works best for those who can't receive standard chemo.

Participant Groups

Group I: Arm C Experimental Treatment 2 Interventions

Participants will receive IV tobemstomig + IV tiragolumab Q3W.

Group II: Arm B Experimental Treatment 1 Intervention

Participants will receive IV tobemstomig Q3W.

Group III: Arm A Active Control 1 Intervention

Participants will receive intravenous (IV) atezolizumab every 3 weeks (Q3W).

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?

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

Findings from Research

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]

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 is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In a phase 2 trial involving 310 patients with metastatic urothelial carcinoma who had previously failed platinum-based chemotherapy, treatment with atezolizumab resulted in a significant overall response rate of 15%, which is notably higher than the historical control rate of 10%.

Atezolizumab demonstrated good tolerability, with only 16% of patients experiencing grade 3-4 treatment-related adverse events, and no treatment-related deaths, indicating it is a safe option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Rosenberg, JE., Hoffman-Censits, J., Powles, T., et al.[2022]

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]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

Atezolizumab is an immunotherapy that effectively enhances T-cell activity against cancer by blocking the PD-L1/PD-1 interaction, which is crucial for tumor cells to evade the immune system.

It has been shown to be well tolerated in phase I trials with no dose-limiting toxicities and has received FDA approval for treating platinum-resistant metastatic non-small cell lung cancer and urothelial cancer, demonstrating significant improvements in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A novel PD-L1 inhibitor in cancer therapy with a focus in bladder and non-small cell lung cancers. Krishnamurthy, A., Jimeno, A.[2019]

References

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

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

2. France pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]

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

Atezolizumab: First Global Approval. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. [2022]

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

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Atezolizumab: A novel PD-L1 inhibitor in cancer therapy with a focus in bladder and non-small cell lung cancers. [2019]