Immunotherapy Combinations for Bladder Cancer

Recruiting at 52 trial locations

Overseen By Reference Study ID Number: WO39613 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Chemotherapy, Hormonal therapy, others

Disqualifiers: Autoimmune disease, CNS metastases, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 5-7 years

272 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting the study. Specifically, you must not have taken any investigational therapy, systemic immunostimulatory agents, or systemic immunosuppressive medication within a specified period before the study begins. If you are on these types of medications, you may need to stop them before participating.

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 whose cancer progressed after platinum-based chemotherapy. It is also effective as a first-line treatment for patients ineligible for cisplatin, with a 24% response rate and 57% one-year survival. ^{1 2 3 4 5}

Is atezolizumab safe for treating bladder cancer?

Atezolizumab has been shown to have a favorable safety profile in patients with advanced bladder cancer, with manageable side effects compared to traditional chemotherapy. It is generally well-tolerated, with fewer severe side effects than chemotherapy, making it a safer option for many patients. ^{1 2 3 6 7}

What makes the drug combination for bladder cancer unique?

This treatment combines multiple drugs, including atezolizumab, which is an immunotherapy that blocks PD-L1 to enhance the immune system's ability to fight cancer. Atezolizumab has shown durable responses and a favorable safety profile compared to traditional chemotherapy, making it a novel option for patients who have progressed after platinum-based treatments or are ineligible for cisplatin. ^{1 2 4 8 9}

What is the purpose of this trial?

A Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with MIBC and in participants with locally advanced or metastatic Urothelial Carcinoma (UC) who have progressed during or following a platinum-containing regimen. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population (e.g., with regard to prior anti-cancer treatment or biomarker status). Participants in the mUC Cohort who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen for Stage 2.

Eligibility Criteria

This trial is for adults with advanced bladder cancer who've had disease progression after one platinum-based treatment. They must be in good physical condition, have proper organ function, and not have HIV or hepatitis. A tumor sample for testing and measurable disease are required. Participants need to agree to use birth control methods.

Inclusion Criteria

I can provide a sample of my tumor for PD-L1 and other tests.

For women of childbearing potential: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating eggs

Negative HIV test at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various immunotherapy-based treatments and combinations, including Atezolizumab, Tiragolumab, Enfortumab Vedotin, and others, until unacceptable toxicity or loss of clinical benefit.

Approximately 5-7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including pCR, ADA presence, RFS, DCR, OS, DOR, EFS, and PFS.

Approximately 5-7 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if they experience loss of clinical benefit or unacceptable toxicity during Stage 1.

Treatment Details

Interventions

• Atezolizumab
• Cisplatin
• Enfortumab Vedotin
• Gemcitabine
• Magrolimab (Hu5F9-G4)
• Niraparib
• Sacituzumab Govitecan
• Tiragolumab
• Tocilizumab

Trial Overview The study tests multiple immunotherapy drugs (like Atezolizumab) and combinations on bladder cancer that's spread or can't be removed by surgery. It adapts over time, introducing new treatments and removing those less effective or too harmful.

Participant Groups

Group I: Cisplatin-eligible MIBC Cohort 3 Arm 2 Experimental Treatment 4 Interventions

Participants will receive Atezolizumab, Tiragolumab (Tira), Cisplatin and Gemcitabine for 3 cycles pre-surgery and 14 cycles of Atezolizumab and Tiragolumab (Tira) post-surgery.

Group II: Atezolizumab + Tocilizumab for mUC Cohort (Stage 1) Experimental Treatment 2 Interventions

Participants will receive atezolizumab and Tocilizumab (TCZ) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

Group III: Atezolizumab + Tiragolumab for mUC Cohort (Stage 1) Experimental Treatment 2 Interventions

Participants will receive atezolizumab and Tiragolumab (Tira) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

Group IV: Atezolizumab + Tiragolumab for Cisplatin-ineligible MIBC Cohort 2 PD-L1- Arm 2 Experimental Treatment 2 Interventions

Participants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery.

Group V: Atezolizumab + Tiragolumab for Cisplatin-ineligible MIBC Cohort 1 PD-L1+ Arm 2 Experimental Treatment 2 Interventions

Participants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery.

Group VI: Atezolizumab + Sacituzumab Govitecan for mUC Cohort (Stage 2) Experimental Treatment 2 Interventions

Participants will receive atezolizumab and Sacituzumab Govitecan (SG) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

Group VII: Atezolizumab + Sacituzumab Govitecan for mUC Cohort (Stage 1) Experimental Treatment 2 Interventions

Participants will receive atezolizumab and Sacituzumab Govitecan (SG) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

Group VIII: Atezolizumab + RO7122290 for mUC Cohort (Stage 1) Experimental Treatment 1 Intervention

Participants will receive atezolizumab and RO7122290 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

Group IX: Atezolizumab + Niraparib for mUC Cohort (Stage 1) Experimental Treatment 2 Interventions

Participants will receive atezolizumab and Niraparib (Nira) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

Group X: Atezolizumab + Magrolimab for mUC Cohort (Stage 1) Experimental Treatment 2 Interventions

Participants will receive atezolizumab and magrolimab (Hu5F9-G4) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

Group XI: Atezolizumab + Enfortumab Vedotin for mUC Cohort (Stage 2) Experimental Treatment 2 Interventions

Participants will receive atezolizumab and Enfortumab Vedotin (EV) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

Group XII: Atezolizumab + Enfortumab Vedotin for mUC Cohort (Stage 1) Experimental Treatment 2 Interventions

Participants will receive atezolizumab and Enfortumab Vedotin (EV) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

Group XIII: Cisplatin-eligible MIBC Cohort 3 Arm 1 Active Control 3 Interventions

Participants will receive 3 cycles of Atezolizumab, Cisplatin, and Gemcitabine pre-surgery and 14 cycles of Atezolizumab only post-surgery.

Group XIV: Atezolizumab for Cisplatin-ineligible MIBC Cohort 2 PD-L1- Arm 1 Active Control 1 Intervention

Participants will receive Atezolizumab for 3 cycles pre-surgery and 14 cycles post-surgery.

Group XV: Atezolizumab for Cisplatin-ineligible MIBC Cohort 1 PD-L1+ Arm 1 Active Control 1 Intervention

Participants will receive Atezolizumab for 3 cycles pre-surgery and 14 cycles post-surgery.

Group XVI: Atezolizumab for mUC Cohort (Stage 1) Active Control 1 Intervention

Participants will receive atezolizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.

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

Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas

Collaborator

Trials

1

Recruited

270+

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, 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]

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]

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]

In a long-term follow-up of patients with metastatic urothelial carcinoma (mUC) who had previously undergone platinum-based chemotherapy, atezolizumab showed a 24-month overall survival (OS) rate of 23%, compared to 13% for those receiving chemotherapy, indicating a potential for durable remission.

Patients treated with atezolizumab experienced fewer severe treatment-related adverse events (43% for chemotherapy vs. 22% for atezolizumab), suggesting a better safety profile, although atezolizumab was associated with more mild adverse events of special interest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Versus Chemotherapy in Patients with Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: A Long-term Overall Survival and Safety Update from the Phase 3 IMvigor211 Clinical Trial. van der Heijden, MS., Loriot, Y., Durán, I., et al.[2022]

Atezolizumab, an anti-PD-L1 therapy, showed significant efficacy in treating metastatic urothelial carcinoma (mUC) patients who had progressed after platinum-based chemotherapy, with objective response rates and overall survival benefits observed across all treatment lines in a study of 315 patients.

The treatment was found to be safe and well-tolerated, with no significant differences in efficacy or adverse effects based on the number of prior therapies, indicating its potential as a viable option for patients regardless of their treatment history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens. Perez-Gracia, JL., Loriot, Y., Rosenberg, JE., 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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]

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

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

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

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

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

Atezolizumab in Patients with Pretreated Urothelial Cancer: a Korean Single-Center, Retrospective 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. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab Versus Chemotherapy in Patients with Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: A Long-term Overall Survival and Safety Update from the Phase 3 IMvigor211 Clinical Trial. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens. [2022]

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

[Immunotherapy for Bladder Cancer]. [2019]