Immunotherapy Combinations for Bladder Cancer

Not currently recruiting at 56 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores different combinations of immunotherapy treatments for bladder cancer, focusing on muscle-invasive bladder cancer (MIBC) and advanced urothelial carcinoma, a type of urinary tract cancer. The researchers aim to identify the most effective drug combinations for patients whose cancer has progressed after initial treatment. The trial divides participants into groups to test various combinations of drugs, such as Atezolizumab (an immunotherapy drug) and Cisplatin. Patients with bladder cancer that has worsened after platinum-based treatment and have a tumor suitable for biopsy might be a good fit. As a Phase 1/Phase 2 trial, it seeks to understand how the treatment works in people and measure its effectiveness in an initial group, offering patients a chance to contribute to groundbreaking research.

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.

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

Research has shown that atezolizumab, a main treatment in this study, is generally safe for people with advanced bladder cancer. In a study with 429 patients, atezolizumab helped shrink tumors in many cases without causing new safety concerns. The FDA has already approved the drug for this type of cancer, indicating a known safety record.

When combined with atezolizumab, tiragolumab has shown promise in controlling bladder cancer. Although still under investigation, early results suggest it is safe.

Enfortumab vedotin, used with atezolizumab, has been compared to standard chemotherapy. Research suggests it has manageable side effects and can help patients live longer.

For those receiving atezolizumab with cisplatin and gemcitabine, studies have shown mixed safety results. However, cisplatin has long been a standard treatment, so its side effects are well-known.

Atezolizumab is also being tested with other treatments like tocilizumab and sacituzumab govitecan. While specific data on these combinations aren't detailed here, tocilizumab is already used for other conditions, and sacituzumab govitecan has shown manageable side effects in past studies.

Overall, these treatments are being tested for safety and effectiveness. Early trials mean side effects are still being studied, but FDA approvals and past research suggest these drugs are reasonably safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the investigational treatments for bladder cancer because they combine different immunotherapies and targeted therapies that offer new ways to fight the disease. Unlike the standard treatments, which often include chemotherapy drugs like Cisplatin and Gemcitabine, these investigational treatments use combinations like Atezolizumab, an immune checkpoint inhibitor, with Tiragolumab, a novel anti-TIGIT antibody, to potentially enhance the immune response against cancer cells. Another approach involves Enfortumab Vedotin, an antibody-drug conjugate that targets and delivers cytotoxic agents directly to cancer cells, minimizing damage to healthy tissue. These novel combinations could offer improved outcomes and fewer side effects compared to current standard therapies.

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

Research shows that atezolizumab, a type of immunotherapy, holds promise for treating bladder cancer. Studies have found it can help patients with urothelial carcinoma, a form of bladder cancer, live longer and slow the disease's progression. In this trial, participants in different arms will receive various treatment combinations. Some will receive atezolizumab combined with tiragolumab, which has provided lasting benefits for some patients. Others will receive enfortumab vedotin with atezolizumab, which significantly extended survival compared to standard treatments. Participants receiving cisplatin and gemcitabine along with atezolizumab may achieve better results in treating bladder cancer. Lastly, combining sacituzumab govitecan with atezolizumab may enhance the effectiveness of these drugs in advanced bladder cancer. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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.

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11983893/

Efficacy and safety of atezolizumab in the treatment ... Immunomodulatory effects and improved outcomes with cisplatin- versus carboplatin-based chemotherapy plus Atezolizumab in urothelial cancer.

2. urotoday.com urotoday.com/conference-highlights/asco-gu-2023/asco-gu-2023-bladder-cancer/142543-asco-gu-2023-atezolizumab-platinum-gemcitabine-vs-placebo-platinum-gemcitabine-for-first-line-treatment-of-locally-advanced-or-metastatic-urothelial-carcinoma-final-os-from-the-randomized-phase-3-imvigor130-study.html

ASCO GU 2023: Atezolizumab + Platinum/gemcitabine vs ... As seen with prior exploratory data, improved OS with atezolizumab + platinum/gemcitabine was greater when patients received cisplatin vs ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.LBA440

Atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs ... In exploratory analyses, OS improved when atezo was combined with cisplatin (cis) vs carboplatin (carbo) regardless of PD-L1 status. Here, we ...

4. esmoopen.com esmoopen.com/article/S2059-7029(24)01742-3/fulltext

final analysis from the phase II IMvigor210 trial The IMvigor210 trial demonstrated clinical benefit and manageable toxicity with atezolizumab monotherapy [anti-programmed death-ligand 1 (PD-L1)] ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666379124000028

versus carboplatin-based chemotherapy plus atezolizumab ... The IMvigor130 trial reveals more favorable effects with atezolizumab combined with gemcitabine and cisplatin (GemCis) versus gemcitabine and carboplatin ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03737123

Study Details | NCT03737123 | Trial of Atezolizumab Plus ... This is a single arm phase II study assessing the activity of atezolizumab in combination with carboplatin + gemcitabine or docetaxel compared to historical ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0305737220301109

Clinical evidence for the first-line treatment of advanced ... Patients with advanced urothelial carcinoma (UC) have poor outcomes, with 5-year survival rates of <5% for those with metastatic, stage IV disease.