Cabozantinib + Avelumab for Bladder Cancer

Not currently recruiting at 319 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Platinum-based chemotherapy

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Autoimmune disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding cabozantinib, a drug that may stop cancer cells from growing by blocking certain enzymes, to avelumab, an immunotherapy drug, is more effective than using avelumab alone for treating metastatic bladder cancer. The combination might shrink the cancer more or prevent its recurrence. Individuals with advanced bladder cancer who have already undergone some chemotherapy may be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use immunosuppressive medication within 7 days before starting the trial, except for certain low-dose steroids and premedication for allergies. You also cannot use certain blood thinners like warfarin, but some others are allowed if stable.

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

Previous studies have shown that avelumab is well-tolerated by patients. Most side effects were mild to moderate, with some experiencing tiredness and infusion-related reactions. Research also shows that cabozantinib is generally safe but can cause more serious side effects. In past trials, 43% to 67% of patients experienced serious side effects, such as increased liver enzymes and high blood pressure.

Both treatments have been studied before, providing some confidence in their safety. The current trial examines how they work together to treat bladder cancer. While both have shown effectiveness, it is important to be aware of the potential for more severe side effects with cabozantinib. Trial participants will be closely monitored to manage any side effects that occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Researchers are excited about these treatments because they combine avelumab, an immune checkpoint inhibitor, with cabozantinib, a tyrosine kinase inhibitor, offering a dual approach to tackling bladder cancer. Unlike most current treatments like chemotherapy or standalone immunotherapy, this combination aims to both activate the immune system and directly inhibit cancer cell growth. This dual mechanism might enhance the effectiveness and potentially improve outcomes for patients with bladder cancer, making it a promising option to explore in the fight against the disease.

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

Research has shown that avelumab, a type of immunotherapy, helps the body's immune system fight cancer and has shown promise in slowing the spread of urothelial cancer. In this trial, some participants will receive avelumab alone. Cabozantinib is another drug that blocks certain enzymes aiding cancer growth. In a study with 19 patients whose urothelial cancer had spread, cabozantinib helped shrink tumors in 42% of them. Other studies have demonstrated that cabozantinib can be effective even when other treatments fail. In this trial, another group of participants will receive a combination of avelumab and cabozantinib, which might further slow cancer growth or prevent it from worsening. ^{1 3 6 7 8}

Who Is on the Research Team?

Shilpa Gupta

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

Adults with advanced or metastatic urothelial cancer who've had one round of platinum-based chemo can join this trial. They must have stable health, no recent major surgeries, and not be on certain blood thinners or immunosuppressants. Women must test negative for pregnancy and all participants should use birth control to prevent pregnancy during the study.

Inclusion Criteria

Your hemoglobin level is at least 8 grams per deciliter.

The amount of protein in your urine is within a certain range.

I don't have active brain metastases and am stable if previously treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle, with or without cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months.

24 months

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 30 days through 90 days, then every 3 months for 5 years.

5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Cabozantinib S-malate

Trial Overview The MAIN-CAV Study is testing if adding Cabozantinib to Avelumab improves treatment outcomes in metastatic urothelial cancer compared to Avelumab alone. It's a phase III trial where patients are randomly assigned to either receive both drugs or just the immunotherapy drug.

How Is the Trial Designed?

Group I: Arm B (avelumab, cabozantinib) Experimental Treatment 8 Interventions

Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.

Group II: Arm A (avelumab) Active Control 7 Interventions

Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cabozantinib combined with nivolumab (CaboNivo) and with ipilimumab (CaboNivoIpi) showed manageable safety profiles, with 75% and 87% of patients experiencing grade 3 or 4 treatment-related adverse events, respectively, including fatigue and hypertension.

The treatment demonstrated promising efficacy, with an overall response rate of 30.6% and a median overall survival of 12.6 months for all patients, while patients with metastatic urothelial carcinoma had even better outcomes, with a median overall survival of 25.4 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors. Apolo, AB., Nadal, R., Girardi, DM., et al.[2023]

Avelumab maintenance therapy after platinum-based chemotherapy in advanced urothelial carcinoma significantly improves overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), especially in patients with PD-L1 positive tumors, compared to those receiving best supportive care.

While avelumab is effective, it is associated with a high rate of treatment-related adverse events (TRAEs) in 86.7% of patients, with 32.4% experiencing severe adverse events, indicating the need for careful patient monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes. Ten Eyck, JE., Kahlon, N., Masih, S., et al.[2022]

Avelumab demonstrated antitumor activity in patients with platinum-refractory metastatic urothelial carcinoma, achieving a complete or partial response in 17% of treated patients, including 6% with complete responses.

The safety profile of avelumab was manageable, with most treatment-related adverse events being mild (grade 1-2), although there were serious adverse events in 8% of patients, including one treatment-related death from pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Patel, MR., Ellerton, J., Infante, JR., et al.[2022]

In a study of 204 patients with advanced urothelial carcinoma, those receiving maintenance avelumab therapy showed longer overall survival compared to those receiving second-line pembrolizumab or cytotoxic chemotherapy, although progression-free survival was not significantly different.

Patients who started maintenance avelumab therapy within 6 weeks of completing first-line chemotherapy had a higher disease control rate (77%) compared to those who waited longer, suggesting that early initiation of avelumab may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. Miyake, M., Shimizu, T., Oda, Y., et al.[2023]

Citations

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Exelixis Announces Updated Phase 1 Trial Results for ... Results among 19 previously treated metastatic urothelial carcinoma (mUC) patients demonstrated a 42% objective response rate (ORR), 12.8 month median ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.17_suppl.LBA4505

A randomised, double blind, phase II clinical trial of ... Secondary endpoints included overall survival (OS), response rate, maximum percentage decrease in measurable disease, safety and tolerability.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8236112/

Cabozantinib and peripheral immunity in advanced urothelial ... Our study demonstrates that cabozantinib has clinical activity and leads to responses in patients with advanced platinum-refractory mUC. The ...

4. 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 ...

5. urotoday.com urotoday.com/conference-highlights/asco-2022/asco-2022-bladder-cancer/137606-asco-2022-cabozantinib-c-in-combination-with-atezolizumab-a-in-urothelial-carcinoma-uc-results-from-cohorts-3-4-5-of-the-cosmic-021-study.html

Results From Cohorts 3, 4, 5 of the COSMIC-021 Study Of the 30 patients in that cohort, there was a 27% overall response rate with two complete responses, and the median progression-free survival ...

6. cabometyxhcp.com cabometyxhcp.com/rcc-treatment/monotherapy/safety

CABOSUN & METEOR show similar safety results for ... Laboratory abnormalities occurring in ≥25% of patients in the CABOMETYX arm of the METEOR trial · Grade 3-4 adverse reactions (ARs) occurring in >1% of patients ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02233

Final Results From a Phase I Trial and Expansion Cohorts ... We report an overall response rate of 38%, with notable efficacy in rare tumor types, such as penile carcinoma, bladder adenocarcinoma, and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12058374/

COSMIC-021 Phase Ib Study of Cabozantinib Plus ... Grade 3 or 4 treatment-related adverse events (TRAEs) were experienced by 43%, 67%, 57%, and 45% of patients, respectively. TRAEs led to ...