Atezolizumab + Cisplatin + Gemcitabine for Bladder Cancer

Recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Immunostimulatory agents

Disqualifiers: Heart disease, Autoimmune disease, Infections, 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: 10

54 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety of the study drug, atezolizumab, when combined with the standard chemotherapy drugs, gemcitabine and cisplatin (or GC). This study will help researchers begin to understand whether combining GC with atezolizumab is better, the same, or worse than the usual approach of using GC alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain medications like systemic immunosuppressive drugs or investigational agents close to the start of the trial. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug combination Atezolizumab, Cisplatin, and Gemcitabine for bladder cancer?

Atezolizumab has shown promising results in treating advanced bladder cancer, especially in patients who cannot use cisplatin, with response rates of up to 24% and improved survival rates. It works by boosting the immune system to fight cancer cells, and has been approved for use after other treatments fail. Cisplatin and Gemcitabine are standard chemotherapy drugs that have been used for bladder cancer, and combining them with Atezolizumab may enhance treatment effectiveness. ^{1 2 3 4 5}

Is the combination of Atezolizumab, Cisplatin, and Gemcitabine safe for treating bladder cancer?

Atezolizumab has shown a favorable safety profile in treating 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 patients who have already received platinum-based treatments. ^{1 3 5 6 7}

How is the drug combination of Atezolizumab, Cisplatin, and Gemcitabine unique for treating bladder cancer?

This drug combination is unique because Atezolizumab, an immune checkpoint inhibitor, enhances the body's immune response against cancer cells, offering a new approach compared to traditional chemotherapy alone. It is particularly beneficial for patients who cannot tolerate cisplatin, providing an effective alternative with a favorable safety profile. ^{1 3 4 5 8}

Research Team

Samuel Funt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with bladder cancer that's invasive but hasn't been treated with chemotherapy or immunotherapy can join. They need to have a certain level of organ function, no severe allergies to the drug components, and agree to biopsies. Pregnant women and those with recent serious infections or heart issues cannot participate.

Inclusion Criteria

You have a low count of a certain type of white blood cells called neutrophils.

You have a sufficient amount of a type of white blood cell called lymphocytes.

Your hemoglobin level is at least 9.0 grams per deciliter.

Exclusion Criteria

I have had chemotherapy before.

You are allergic to Chinese hamster ovary cell products or any part of the atezolizumab medication.

I have had a stem cell or organ transplant in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive combination therapy with gemcitabine, cisplatin, and atezolizumab on a 21-day cycle for 6 cycles

18 weeks

6 cycles of treatment

Phase 2 Treatment

Participants receive a single dose of atezolizumab followed by combination therapy on a 21-day cycle for 4 cycles, then another single dose of atezolizumab

12 weeks

4 cycles of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Atezolizumab
• Cisplatin
• Gemcitabine

Trial Overview The trial is testing if adding Atezolizumab (an immune system booster) to standard chemo drugs Gemcitabine and Cisplatin before surgery helps more than chemo alone. It's in phase II, so they're looking at how safe it is and how well it works.

Participant Groups

Group I: Atezolizumab, Gemcitabine, Cisplatin Experimental Treatment 3 Interventions

This is a two phase study with a single study arm for each phase. For Phase 1: Following enrollment participants will be treated with combination therapy on a 21 day cycle x 6 cycles. Gemcitabine (1000 mg/m2 on Day 1 and Day 8), cisplatin (70 mg/m2 on Day 1), and atezolizumab (1200 mg on Day 8) will be administered intravenously. Phase 2: Following enrollment participants will be treated with a single dose of atezolizumab alone followed by combination therapy on a 21-day cycle x 4 cycles, followed by a single dose of atezolizumab alone. Gemcitabine 1000mg/m2, cisplatin (70 mg/m2 on Day 1), and atezolizumab (1200 mg on Day 8) will be administered intravenously.

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+

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

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, 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 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 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 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, 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]

References

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

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]

2. France pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

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. 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]

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

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