Atezolizumab for High-Risk Bladder Cancer

(IMvigor011 Trial)

Recruiting at 262 trial locations

Overseen By Reference Study ID Number: BO42843 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Chemotherapy, Hormonal therapy

Disqualifiers: Pregnancy, HIV, Hepatitis, Tuberculosis, others

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

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: 12

Duration: 12 months

761 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with placebo in participants with MIBC who are ctDNA positive and are at high risk for recurrence following cystectomy.

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 have had any anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks before joining the study. Hormone-replacement therapy or oral contraceptives are allowed.

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

Atezolizumab has shown effectiveness in treating advanced bladder cancer, with a 15% response rate and 36% one-year survival in patients whose cancer progressed after initial chemotherapy. It is also well-tolerated, making it a promising option for those with high-risk bladder cancer. ^{1 2 3 4 5}

Is atezolizumab safe for humans?

Atezolizumab, also known as Tecentriq, has been shown to have a favorable safety profile in patients with advanced bladder cancer, meaning it is generally well-tolerated by humans. ^{1 5 6 7 8}

How does the drug atezolizumab differ from other treatments for high-risk bladder cancer?

Atezolizumab is unique because it is a monoclonal antibody that blocks the PD-L1 protein, which helps the immune system attack cancer cells more effectively. Unlike traditional chemotherapy, it specifically targets immune checkpoints, potentially leading to better response rates and survival in patients with advanced bladder cancer, especially those with high PD-L1 expression. ^{1 3 4 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with high-risk muscle-invasive bladder cancer who've had their bladders surgically removed and are positive for ctDNA, indicating a risk of recurrence. They should be fully recovered from surgery, have a life expectancy of at least 12 weeks, and agree to use contraception if applicable. Exclusions include active tuberculosis, severe allergies to certain substances, autoimmune diseases (with some exceptions), other recent cancer therapies or clinical trials.

Inclusion Criteria

My tumor has been tested and shows PD-L1 protein.

I have fully recovered from bladder removal surgery within the last 6 months.

My blood test shows I have cancer-related genetic changes.

Exclusion Criteria

History of severe allergic, anaphylactic, or other hypersensitivity reactions to specified substances

I have been tested and do not have active tuberculosis.

I have active hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab or placebo intravenously on Day 1 of each 28-day cycle for up to 12 cycles or 1 year

12 months

12 visits (in-person, every 28 days)

Follow-up

Participants are monitored for disease recurrence, survival, and quality of life

Up to 10 years

Treatment Details

Interventions

• Atezolizumab
• Placebo

Trial Overview The study compares the effectiveness and safety of Atezolizumab (a type of immunotherapy) against a placebo in preventing cancer recurrence after bladder removal surgery. Participants will be randomly assigned to receive either Atezolizumab or a placebo without knowing which one they're getting (double-blind).

Participant Groups

Group I: Arm C: Surveillance Follow-Up Experimental Treatment 1 Intervention

Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter follow-up.

Group II: Arm A: Atezolizumab Experimental Treatment 2 Interventions

Atezolizumab will be administered intravenously at a dose of 1680 milligrams (mg) on Day 1 of each 28-day cycle for 12 cycles or up to 1 year (whichever occurs first). Atezolizumab will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.

Group III: Arm B: Placebo Placebo Group 2 Interventions

Placebo will be administered intravenously on Day 1 of each 28-day cycle. Placebo will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.

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

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

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, 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 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]

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 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]

References

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

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

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

Spotlight on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer. [2020]

3. France pubmed.ncbi.nlm.nih.gov

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

4. 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]

5. France pubmed.ncbi.nlm.nih.gov

Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies. [2019]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Pretreated Urothelial Cancer: a Korean Single-Center, Retrospective Study. [2022]

7. 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]

8. Poland pubmed.ncbi.nlm.nih.gov

Disease control with prior platinum-based chemotherapy is prognostic for survival in patients with metastatic urothelial cancer treated with atezolizumab in real-world practice. [2022]

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

Atezolizumab: First Global Approval. [2019]

10. 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]