Immunotherapy for Bladder Cancer

Not currently recruiting at 137 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a new immunotherapy drug, tobemstomig (an anti-PD-1/anti-LAG-3 bispecific antibody), alone or with another drug, tiragolumab, in people with advanced bladder cancer. It compares these treatments to atezolizumab, an existing option. The trial targets individuals who haven't received chemotherapy for their advanced bladder cancer and can't take platinum-based chemotherapy. Participants should have bladder cancer symptoms that affect daily life and must have advanced or metastatic urothelial cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Previous studies have shown that tobemstomig, a treatment targeting specific proteins on cancer cells, is well-tolerated both alone and with other treatments. Reports indicate it generally causes only mild side effects, such as fatigue and mild skin reactions. When combined with tiragolumab, which blocks another cancer pathway, the safety profile remains positive, with no severe side effects reported so far.

Atezolizumab, another treatment in this trial, has already received approval for certain cancers and is known to be safe. Most people tolerate it well, though some experience tiredness, nausea, and itching.

Overall, the safety data for tobemstomig, its combination with tiragolumab, and atezolizumab are reassuring. Most side effects have been mild and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they offer innovative approaches beyond the standard chemotherapy and immune checkpoint inhibitors currently available. RO7247669 is unique because it targets specific proteins involved in cancer cell growth, potentially leading to more precise treatment. Tiragolumab works differently by blocking a checkpoint pathway called TIGIT, which may enhance the immune system’s ability to fight cancer. These new mechanisms of action could mean more effective treatments with fewer side effects for patients.

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

Research has shown that tobemstomig, a new treatment under study in this trial, targets proteins called PD-1 and LAG-3, which help the immune system fight cancer. Participants may receive tobemstomig alone or with tiragolumab, which targets another protein called TIGIT, potentially enhancing the immune response against cancer. These treatments remain experimental and are being compared to atezolizumab, which participants in another trial arm will receive. Atezolizumab is already known to help some bladder cancer patients. The aim is to determine if the new treatments can improve outcomes for those unable to undergo certain chemotherapies. ^{2 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-LaRoche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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, 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]

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]

Citations

1. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/bladder-cancer/a-study-of-ro7247669-alone-or-in-combination-with-tirag-35445.html

Clinical study; locally advanced or metastatic urothelial... This study is comparing the effects of tobemstomig alone or in combination with tiragolumab in comparison with atezolizumab in people with bladder cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05645692?utm_source=trialradar

A Study Evaluating Different Immunotherapies (LAG-3 and ... This study will evaluate the safety of tobemstomig alone or in combination with tiragolumab compared with atezolizumab in participants with previously ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10968461/

Revisiting Treatment of Metastatic Urothelial Cancer We review the working definitions of 'cisplatin ineligibility' and 'platinum ineligibility' in mUC clinical trials and the standard of care in both categories.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04140500

NCT04140500 | Dose Escalation Study of a PD1-LAG3 ... This is a first-in-human, open-label, multicenter, Phase I multiple-ascending dose (MAD) study of RO7247669, an anti PD-1 (programmed death-1) and LAG-3 ...

5. forpatients.roche.com forpatients.roche.com/content/patient-platform/global/en/trials/cancer/bladder-cancer/a-study-of-ro7247669-alone-or-in-combination-with-tirag-35445.pdf

A Study Evaluating Different Immunotherapies (LAG-3 and PD-1 Tobemstomig, an anti-PD-1 and ant-LAG-3 bispecific antibody, and tiragolumab, an anti-TIGIT monoclonal antibody, are experimental medicines, which means ...

6. forpatients.roche.com forpatients.roche.com/en/trials/cancer/bladder-cancer/a-study-of-ro7247669-alone-or-in-combination-with-tirag-35445.html

Clinical study; locally advanced or metastatic urothelial... This study aims to assess the safety of tobemstomig alone or in combination with tiragolumab compared with atezolizumab in people with previously untreated, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10667103/

and LAG-3-targeting bispecific molecule tebotelimab in solid ... The bispecific molecule tebotelimab, which blocks both PD-1 and LAG-3, is well tolerated as a monotherapy and in combination with the anti-HER-2 antibody ...

8. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/dose-escalation-study-of-a-pd1-lag3-bispecific-antibody-65890.html

AN OPEN LABEL, MULTICENTER, DOSE ESCALATION ... It blocks the activity of PD-1 and another element that cancer cells can use to hide from the immune system called 'LAG-3'. By blocking PD-1 and LAG-3 at ...

9. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1047610/full

PD-1/LAG-3 bispecific antibody potentiates T cell activation ... The BsAb YG-003D3 has good anti-tumor activity, which is expected to become a novel drug candidate for cancer immunotherapy.