Atezolizumab + Cisplatin + Gemcitabine for Bladder Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination to improve bladder cancer treatment. Researchers are evaluating the safety and effectiveness of adding atezolizumab (an immunotherapy drug) to the standard chemotherapy drugs, cisplatin and gemcitabine. The goal is to determine if this combination outperforms the standard treatment alone. Individuals with advanced bladder cancer who have not received chemotherapy for it may qualify for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

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

Studies have shown that combining atezolizumab with gemcitabine and cisplatin is generally well-tolerated. Research indicates that 48.5% of patients responded positively to this treatment, demonstrating its effectiveness for many.

The safety of this combination has also been studied, revealing a manageable safety profile. No unexpected serious side effects emerged, suggesting the treatment is relatively safe.

Overall, these findings suggest the treatment is generally well-tolerated, though individual experiences may vary. Participants should discuss any concerns with the trial team and their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab, cisplatin, and gemcitabine for bladder cancer because it introduces a novel approach to treatment. Atezolizumab is an immunotherapy drug that works by targeting and blocking the PD-L1 protein, helping the immune system to attack cancer cells more effectively. This is different from the standard chemotherapy options, like cisplatin and gemcitabine alone, which primarily kill cancer cells directly. By combining immunotherapy with chemotherapy, there is potential for enhanced effectiveness and a broader attack on the cancer cells, offering hope for improved outcomes for patients.

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

Research has shown that using atezolizumab with cisplatin and gemcitabine can effectively treat bladder cancer. In this trial, participants will receive this combination therapy. Studies have found that patients receiving this combination often achieve better results compared to those taking gemcitabine and carboplatin. Specifically, the IMvigor130 trial demonstrated that this combination improved overall survival rates. Atezolizumab enhances the immune system's ability to find and attack cancer cells. Adding cisplatin and gemcitabine, common chemotherapy drugs, boosts this effect. ^{1 5 6 7 8}

Who Is on the Research Team?

Samuel Funt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

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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 ...

4. 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 ( ...

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Immunomodulatory effects and improved outcomes with cisplatin The IMvigor130 trial reveals more favorable effects with atezolizumab combined with gemcitabine and cisplatin (GemCis) versus gemcitabine and carboplatin ( ...

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Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in ... The objective of this phase II trial was to evaluate the efficacy and safety of adding atezolizumab to gemcitabine and cisplatin (GC).

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ASCO 2019: A Pilot Safety Study of Gemcitabine and ... Those receiving chemoimmunotherapy had a median progression-free survival of 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months ( ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00358-4/fulltext?rss=yes

interim analysis of a randomised, open-label phase 2 trial Neoadjuvant TAR-200 plus cetrelimab showed a high pathological complete response rate with a manageable safety profile. These results support ...