Tiragolumab + Atezolizumab for Bladder Cancer

Overseen By Padmanee Sharma, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antibiotics, Immunosuppressants, Immunostimulants

Disqualifiers: Autoimmune disease, Cardiovascular disease, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if the combination of atezolizumab and tiragolumab can help to control bladder cancer when it is given before surgery to remove the bladder and tumor.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive medication or certain other treatments, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

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

Atezolizumab, one of the drugs in the combination, has shown effectiveness in treating advanced bladder cancer, with response rates of up to 24% and improved survival rates in patients who were not eligible for certain chemotherapies. It works by boosting the immune system's ability to fight cancer cells. ^{1 2 3 4 5}

Is the combination of Tiragolumab and Atezolizumab safe for treating bladder cancer?

Atezolizumab, used alone, has shown a favorable safety profile in treating advanced bladder cancer, with manageable side effects compared to traditional chemotherapy. While specific safety data for the combination with Tiragolumab is not provided, Atezolizumab's existing safety record is promising. ^{1 2 3 5 6}

How is the drug combination of Tiragolumab and Atezolizumab unique for treating bladder cancer?

The combination of Tiragolumab and Atezolizumab is unique because it targets the PD-L1/PD-1 immune checkpoint, enhancing the body's immune response against bladder cancer. Atezolizumab is already known for its effectiveness in patients who cannot tolerate cisplatin chemotherapy, offering a potentially more effective alternative with a favorable safety profile. ^{1 2 3 4 7}

Research Team

Padmanee Sharma, MD, PhD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with high-risk urothelial carcinoma who can't take cisplatin or refused it, and are fit enough for bladder surgery. They must have good lung function, no severe infections or recent major surgeries, not be on certain medications, and agree to use contraception if applicable. People with active TB, certain heart conditions, other cancers within 5 years, or autoimmune diseases cannot join.

Inclusion Criteria

I am eligible for a surgery aimed at completely removing my cancer.

Negative hepatitis B surface antigen (HBsAg) test at screening

Ability to comply with the study protocol

Exclusion Criteria

I have had a previous transplant of stem cells or an organ.

Treatment with investigational therapy within 42 days prior to study treatment

History of severe allergic anaphylactic reactions to specific agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant treatment with atezolizumab and tiragolumab

6 weeks

3 visits (in-person)

Surgery

Participants undergo surgery to remove the bladder and tumor

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Atezolizumab and Tiragolumab

Trial Overview The study tests whether combining two drugs (Tiragolumab and Atezolizumab) before surgery can better control bladder cancer compared to current treatments. Participants will receive these drugs prior to their planned surgical procedure to remove the tumor.

Participant Groups

Group I: Tiragolumab Experimental Treatment 1 Intervention

Tiragolumab will be administered at a fixed dose of 600 mg intravenously Q3W on Day 1 of each 21-day cycle.

Group II: Atezolizumab Experimental Treatment 1 Intervention

Atezolizumab will be administered at a fixed dose of 1200 mg Q3W (1200 mg on Day 1 of each 21 day cycle),

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

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]

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]

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 has been approved by the FDA as a treatment for advanced bladder cancer, specifically for patients who cannot receive cisplatin chemotherapy.

This approval provides a potentially more effective treatment option compared to carboplatin-based chemotherapy, particularly for frail and elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]

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

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

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

Atezolizumab: First Global Approval. [2019]

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

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]