Cabozantinib + Atezolizumab for Bladder Cancer

(ABATE Trial)

Recruiting at 5 trial locations

Overseen By Gabrielle Tiggs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Deepak Kilari

Must not be taking: Antibiotics, Immunosuppressants, Anticoagulants, others

Disqualifiers: Infections, Transplant history, Autoimmune, 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: 3

Duration: 9 weeks

46 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label phase II study assessing the activity of cabozantinib combined with atezolizumab in patients with resectable muscle-invasive urothelial carcinoma who are ineligible for cisplatin-based therapy or decline cisplatin-based therapy. Each cycle equals 21 days. The dose of atezolizumab is 1200 mg IV flat dose every 3 weeks (Day 1) plus cabozantinib 40 mg orally daily (Day 1 through Day 21). Patients will receive three cycles of treatment prior to cystectomy unless they discontinue treatment for unacceptable toxicity or progressive disease by RECIST v1.1 or withdraw consent.

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 medications like systemic corticosteroids or other immunosuppressive drugs must be stopped 2 weeks 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 been shown to be effective in treating advanced bladder cancer, especially in patients who have not responded to first-line chemotherapy. In clinical trials, it improved response rates and survival compared to other treatments, with a 15% response rate in patients who had previously received chemotherapy and a 24% response rate in those who were chemotherapy-naïve and ineligible for cisplatin. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Atezolizumab safe for humans?

Atezolizumab, used for advanced bladder cancer, has shown a favorable safety profile in studies, with manageable side effects. It has been well-tolerated in patients, with some experiencing mild to moderate side effects. ^{1 2 4 5 6}

How is the drug combination of Cabozantinib and Atezolizumab unique for bladder cancer treatment?

The combination of Cabozantinib and Atezolizumab is unique because it pairs a PD-L1-blocking antibody (Atezolizumab) with a tyrosine kinase inhibitor (Cabozantinib), potentially enhancing the immune response against bladder cancer by blocking immunosuppressive signals and inhibiting cancer cell growth pathways. This approach is different from standard treatments that typically involve chemotherapy or single-agent immunotherapy. ^{1 2 4 7 8}

Research Team

Deepak Kilari

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

Adults with muscle-invasive bladder cancer who can't have or don't want cisplatin-based therapy. They should be fit for surgery, not pregnant, willing to use contraception, and free from HIV/AIDS, severe infections, other active cancers (except certain cases), significant heart disease, and uncontrolled illnesses. Prior treatments and allergies to study drugs are also considered.

Inclusion Criteria

I haven't had radiation therapy in the last 4 weeks, especially not to the bladder.

Must have a life expectancy of at least 12 weeks at registration.

My surgeon agrees I can undergo major bladder surgery.

Exclusion Criteria

I have not received a live vaccine in the last 4 weeks and do not plan to during or within 5 months after the study.

You have a history of severe allergic reactions to certain types of medications, or rare hereditary problems with digesting certain sugars.

Treatment with any investigational drug within 30 days prior to registration.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib 40 mg orally daily and atezolizumab 1200 mg IV every 3 weeks for 3 cycles (9 weeks total) prior to cystectomy

9 weeks

3 visits (in-person) for atezolizumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pathologic response and adverse events

12 months

Long-term follow-up

Participants are monitored for event-free survival, including recurrence of disease or progression

24 months

Treatment Details

Interventions

• Atezolizumab
• Cabozantinib
• Cystectomy

Trial Overview The trial tests cabozantinib taken orally daily combined with atezolizumab given intravenously every three weeks in patients before they undergo cystectomy. The goal is to see how well these drugs work together against bladder cancer when cisplatin isn't an option.

Participant Groups

Group I: Treatment Arm Experimental Treatment 3 Interventions

Cabozantinib 40 mg orally daily x 9 weeks plus Atezolizumab 1200 mg every 3 weeks x 3 doses

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?

Deepak Kilari

Lead Sponsor

Trials

1

Recruited

50+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

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 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 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]

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 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 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]

Atezolizumab is being studied as a neoadjuvant treatment for muscle-invasive bladder cancer (MIBC) in a phase II trial, where it is administered before radical cystectomy to evaluate its effectiveness based on the BASQ classification of tumor subtypes.

The trial aims to determine the objective pathological responses and 1-year progression-free survival rates in patients with MIBC, highlighting the potential of using molecular subtype characteristics to select the most responsive patient groups for atezolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial. Yuk, HD., Jeong, CW., Kwak, C., et al.[2021]

References

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

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer. [2020]

4. 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]

5. France pubmed.ncbi.nlm.nih.gov

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

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

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Swiss experience of atezolizumab for platinum-pretreated urinary tract carcinoma: the SAUL study in real-world practice. [2021]