Atezolizumab + Chemotherapy for Bladder Cancer

Recruiting at 9 trial locations

Overseen By Samuel Funt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

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: Unknown

Duration: 15-24 weeks

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare any good and bad effects the study drug atezolizumab has on the cancer when combined with the standard chemotherapy drugs gemcitabine and cisplatin (or GC) in two different dosing schedules: chemotherapy (GC) before atezolizumab vs. GC after atezolizumab.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain treatments like chemotherapy, immunotherapy, and some herbal therapies must be stopped before starting the trial. It's best to discuss your specific medications with the trial team.

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

Atezolizumab has shown effectiveness in treating advanced bladder cancer, with studies indicating that it can lead to durable tumor responses. In patients whose cancer progressed after initial chemotherapy, the drug had a response rate of 15% and a 1-year survival rate of 36%. It is also effective as a first-line treatment for patients who cannot receive cisplatin, with a response rate of 24% and a 1-year survival rate of 57%. ^{1 2 3 4 5}

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

Atezolizumab, when used for bladder cancer, has shown a favorable safety profile compared to traditional chemotherapy, with fewer severe side effects. Patients treated with Atezolizumab experienced manageable side effects, mostly mild to moderate, and had fewer treatment-related adverse events compared to those receiving chemotherapy. ^{1 2 6 7 8}

How is the drug Atezolizumab + Chemotherapy unique for bladder cancer treatment?

Atezolizumab, combined with chemotherapy, is unique for bladder cancer because it blocks the PD-L1/PD-1 pathway, enhancing the immune system's ability to attack cancer cells, and is effective for patients who cannot tolerate standard cisplatin chemotherapy. It offers a potentially more effective and less toxic alternative for frail or elderly patients compared to traditional chemotherapy options. ^{1 2 4 7 8}

Research Team

Samuel Funt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with advanced bladder cancer that can't be surgically removed or has spread, who haven't had chemotherapy or immunotherapy for metastatic disease. They must have a life expectancy of at least 12 weeks, measurable disease amenable to biopsy, and agree to use effective contraception post-treatment. Excluded are those with prior transplants, heart disease class III/IV, certain recent treatments including investigational drugs and systemic steroids, known liver diseases or bone marrow disorders, active infections like HIV/Hepatitis B/C/TB, severe allergies to specific antibodies or proteins.

Inclusion Criteria

I am fully active or can carry out light work.

Estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73m^2

Life expectancy ≥ 12 weeks

Exclusion Criteria

I haven't had cancer treatment in the last 3 weeks.

I have not had any other cancers in the last 5 years.

I have been treated with drugs targeting PD-1 or PD-L1.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab alone or in combination with gemcitabine and cisplatin in different dosing schedules

15-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Atezolizumab
• Cisplatin
• Gemcitabine

Trial Overview The trial is testing the effectiveness of Atezolizumab (an immune therapy drug) combined with Gemcitabine and Cisplatin (chemotherapy drugs) in two different sequences: one where chemotherapy is given before Atezolizumab and another where it's given after. The goal is to see which sequence works better against metastatic bladder cancer.

Participant Groups

Group I: Atezolizumab with Gemcitabine and Cisplatin Experimental Treatment 3 Interventions

Gemcitabine and Cisplatin for 2 cycles. One treatment cycle equals 21 days. After 2 cycles of Gemcitabine and Cisplatin patient will receive combined atezolizumab and Gemcitabine and Cisplatin for 4 cycles. All 6 treatment cycles will take approximately 18 weeks. If carboplatin is substituted for cisplatin, eGFR for dosing may be calculated by institutional standard formulas, at the discretion of the treating investigator.

Group II: Atezolizumab alone with Gemcitabine and Cisplatin Experimental Treatment 3 Interventions

Atezolizumab alone for 2 cycles. One treatment cycle equals 21 days. Then patient will receive combined atezolizumab and Gemcitabine and Cisplatin for 6 cycles. All 8 treatment cycles will take approximately 24 weeks. If carboplatin is substituted for cisplatin, eGFR for dosing may be calculated by institutional standard formulas, at the discretion of the treating investigator. This cohort is NO LONGER ACCRUING patients since 5/22/2018.

Group III: Atezolizumab alone for 1 cycle prior to gemcitabine, cisplatin Experimental Treatment 3 Interventions

Atezolizumab alone for 1 cycle. One treatment cycle equals 21 days. After 1 cycle of atezolizumab the patients will receive combined atezolizumab and gemcitabine, cisplatin for 4 cycles. All 5 treatment cycles will take approximately 15 weeks. Cisplatin dose can be given on day 1 or split over days 1 and 8 at the investigator"s discretion. Once the split-dose cisplatin is used, it should be used for the remainder of the chemotherapy treatment course.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Targos

Collaborator

Trials

1

Recruited

30+

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]

Atezolizumab, a PD-L1 inhibitor, has shown effectiveness as a first-line treatment for advanced bladder cancer in patients who cannot receive standard cisplatin chemotherapy, according to a phase II study.

Nearly 25% of the patients in the study experienced durable responses to atezolizumab, highlighting its potential as a viable treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Atezolizumab Effective in Bladder Cancer. [2019]

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 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]

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

First-Line Atezolizumab Effective in Bladder Cancer. [2019]

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

Complete remission with immunotherapy: Case report of a patient with metastatic bladder cancer to the humerus. [2020]

6. 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]

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

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

8. 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]