Cabozantinib + Atezolizumab for Bladder Cancer

(ABATE Trial)

Not currently recruiting at 6 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with bladder cancer that has spread into the muscle. It uses two medications, cabozantinib (a targeted therapy) and atezolizumab (an immunotherapy), to determine if they work better together for patients who can't or won't use the standard cisplatin-based therapy. The goal is to see if this combination can shrink the cancer before surgery. People diagnosed with muscle-invasive bladder cancer who can't have cisplatin might be a good fit for this trial. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

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

A previous study used cabozantinib and atezolizumab together to treat cancer. Research shows that this combination has been tested for safety and effectiveness. Patients experienced varied outcomes; some lived longer. However, side effects such as tiredness and diarrhea, common with cancer treatments, were reported.

Atezolizumab alone has improved survival in patients with bladder cancer, making it a helpful treatment option. Cabozantinib has been shown to help the immune system fight tumors.

Since this trial is in its second phase, the treatment has already passed initial safety tests. However, more research is needed to confirm its tolerance. Participants should consult their doctors to understand the possible risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for bladder cancer?

Researchers are excited about the combination of Cabozantinib and Atezolizumab for bladder cancer because it targets the cancer in a unique way. Unlike traditional treatments that might only block cancer growth or boost the immune system separately, Cabozantinib works by inhibiting pathways that help cancer cells grow and spread, while Atezolizumab enhances the immune system's ability to attack cancer cells. This dual approach not only targets the cancer cells more effectively but also has the potential to overcome resistance that might develop with standard therapies. This combination could offer a powerful new option for patients who have limited success with existing treatments.

What evidence suggests that cabozantinib combined with atezolizumab could be an effective treatment for bladder cancer?

In this trial, participants will receive a combination of cabozantinib and atezolizumab. Previous studies have shown that this combination holds promise in treating certain cancers. Specifically, research indicates that patients can live for about 10.6 months without their cancer worsening, allowing many to experience several months without progression. The treatment has also demonstrated a good response rate, with many patients seeing tumor shrinkage. Overall, these findings suggest that cabozantinib and atezolizumab together could effectively treat muscle-invasive urothelial carcinoma, particularly for those who cannot or choose not to use cisplatin-based therapies. ^{1 4 6 7 8}

Who Is on the Research Team?

Deepak Kilari

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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, 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39965176/

COSMIC-021 Phase Ib Study of Cabozantinib Plus ... The median progression-free survival (95% CI) was 5.5 (1.6 to 11.6), 5.6 (3.1 to 11.1), 5.4 (1.6 to 7.6), and 3.0 (1.8 to 5.5) months, ...

2. urotoday.com urotoday.com/conference-highlights/asco-2023/asco-2023-kidney-cancer/144964-asco-2023-efficacy-and-safety-of-atezolizumab-cabozantinib-vs-cabozantinib-alone-after-progression-with-prior-immune-checkpoint-inhibitor-treatment-in-metastatic-rcc-primary-pfs-analysis-from-the-phase-3-randomized-open-label-contact-03-study.html

Efficacy and Safety of Atezolizumab + Cabozantinib vs ... The median progression free survival for atezolizumab + cabozantinib was 10.6 months versus 10.8 months for cabozantinib (HR 1.03, 95% CI 0.83-1.28).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04289779

Study Details | NCT04289779 | Study of CAbozantinib in ... Estimate the pathologic response (PaR) rate to neoadjuvant cabozantinib and atezolizumab in subjects with muscle-invasive urothelial cancer of the bladder.

4. cancernetwork.com cancernetwork.com/view/second-line-cabozantinib-regimens-exhibit-efficacy-in-advanced-rcc

Second-Line Cabozantinib Regimens Exhibit Efficacy in ... Additional efficacy data revealed that in the monotherapy and combination arms, the ORR was 36% vs 37%, all of which consisted of PRs. Among ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01675

COSMIC-021 Phase Ib Study of Cabozantinib Plus ... The median progression-free survival (95% CI) was 5.5 (1.6 to 11.6), 5.6 (3.1 to 11.1), 5.4 (1.6 to 7.6), and 3.0 (1.8 to 5.5) months, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11983893/

Efficacy and safety of atezolizumab in the treatment ... Atezolizumab has demonstrated significant improvements in OS and PFS among patients with UC, offering crucial insights for decision-making in UC immunotherapy.

7. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-kidney-cancer/160954-asco-2025-efficacy-and-safety-of-second-line-cabozantinib-atezolizumab-for-patients-with-advanced-renal-cell-carcinoma-after-progression-on-immuno-oncology-combinations-subgroup-analysis-of-contact-03.html

Subgroup Analysis of CONTACT-03 Among patients who had received 1L IO combination regimens, the median OS was NE (95% CI: 18.3–NE) with cabozantinib and 24.3 months (95% CI: ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.800

A phase 2 study of cabozantinib in combination with ... Cabozantinib (C) has a unique immunomodulatory profile that may foster anti-tumor immunity and has demonstrated clinical activity as monotherapy ...