Cabozantinib + Atezolizumab for Prostate Cancer

Overseen By Susan Sharry

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Utah

Must not be taking: Anticoagulants, Immunosuppressants, Corticosteroids

Disqualifiers: Chemotherapy, Brain metastases, Autoimmune diseases, 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: Unknown

Duration: 21 days per cycle, ongoing until disease progression or unacceptable toxicity

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests whether cabozantinib and atezolizumab work to shrink tumors in patients with castrate-resistant prostate cancer that had spread to other places in the body (metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and atezolizumab may kill more tumor cells in patients with metastatic castrate-resistant prostate cancer.

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 have received certain treatments like chemotherapy, immunotherapy, or kinase inhibitors shortly before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug combination of Cabozantinib and Atezolizumab for prostate cancer?

Research shows that Cabozantinib, when combined with Atezolizumab, has shown promising results in treating metastatic castration-resistant prostate cancer, especially in patients who have limited options after other hormone therapies. Cabozantinib is known to enhance the immune response, which may improve the effectiveness of Atezolizumab, an immune checkpoint inhibitor. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Atezolizumab generally safe for humans?

Atezolizumab has been used in various cancer treatments and is generally considered to have a manageable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include lung inflammation, liver inflammation, and thyroid issues. The safety of Cabozantinib in combination with Atezolizumab specifically for prostate cancer may not be fully established, but both drugs have been used safely in other cancer treatments. ^{6 7 8 9 10}

How is the drug combination of Cabozantinib and Atezolizumab unique for treating prostate cancer?

The combination of Cabozantinib and Atezolizumab is unique because Cabozantinib, a drug that blocks certain proteins involved in cancer growth, works with Atezolizumab, an immune system booster, to potentially enhance the body's ability to fight prostate cancer. This approach is being tested for patients with advanced prostate cancer who have limited treatment options after other therapies. ^{1 2 3 4 11}

Research Team

Umang Swami, MD

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Eligibility Criteria

Men aged 18+ with metastatic castration-resistant prostate cancer that has spread and progressed despite hormone therapy. They must have certain blood, liver, and kidney function levels, agree to contraception use, not have had certain recent treatments or other cancers within 3 years, no severe illnesses or infections, and be able to follow the study plan.

Inclusion Criteria

Serum albumin >= 2.5 g/dl

Lymphocyte count >= 0.5 x 10^9/L (500/uL)

Alkaline phosphatase (ALP) =< 3 × institutional ULN

Exclusion Criteria

My cancer has spread, but I don't have pain or loss of function from it.

I haven't had a live vaccine within 30 days before starting the study treatment.

I have brain metastases or cranial epidural disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib orally once daily on days 1-21 and atezolizumab intravenously on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle, ongoing until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3 months until disease progression or start of another therapy.

Up to 3 years

Treatment Details

Interventions

• Atezolizumab
• Cabozantinib S-malate

Trial Overview The AtezoCab trial is testing if combining cabozantinib (a drug blocking enzymes for cell growth) with atezolizumab (an immunotherapy antibody) can shrink tumors in patients with advanced prostate cancer compared to current standard treatments.

Participant Groups

Group I: Treatment (cabozantinib, atezolizumab) Experimental Treatment 2 Interventions

Patients receive cabozantinib PO QD on days 1-21 and atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 132 patients with metastatic castration-resistant prostate cancer, the combination of cabozantinib and atezolizumab demonstrated an objective response rate of 23%, indicating promising antitumor activity after prior hormonal therapies.

While the treatment showed efficacy, 55% of patients experienced grade 3-4 treatment-related adverse events, with pulmonary embolism and diarrhea being the most common, suggesting that while the combination is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). Agarwal, N., McGregor, B., Maughan, BL., et al.[2022]

Cabozantinib, which inhibits multiple receptor tyrosine kinases, is being evaluated in combination with the PD-L1 inhibitor atezolizumab for its potential to enhance treatment responses in men with metastatic castration-resistant prostate cancer (mCRPC).

A phase III trial (NCT04446117) is being designed to compare the efficacy of cabozantinib plus atezolizumab against a second novel hormone therapy in patients with mCRPC who have previously received hormone treatments, addressing a significant need for effective options in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer. Agarwal, N., Azad, A., Carles, J., et al.[2022]

Cabozantinib, a multitarget tyrosine kinase inhibitor, is effective in treating medullary thyroid cancer, metastatic renal cell carcinoma, and hepatocellular carcinoma, and is now being tested in prostate cancer patients for its potential immunostimulatory effects.

The drug induces immunogenic cell death in prostate cancer cells and alters dendritic cell behavior, suggesting it may enhance the effectiveness of immunotherapy by modifying the immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib. Scirocchi, F., Napoletano, C., Pace, A., et al.[2021]

The combination of cabozantinib and abiraterone was well-tolerated in patients with metastatic castration-resistant prostate cancer (mCRPC), with no dose-limiting toxicities observed at the initial dose levels during the first 4 weeks of treatment.

Preliminary efficacy results showed that the median overall survival was significantly improved at the 40 mg dose of cabozantinib, reaching 39.08 months, compared to 23.29 months at the 20 mg dose, indicating that 40 mg is the recommended phase 2 dose (RP2D) for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dose finding clinical trial of cabozantinib (XL184) administered in combination with abiraterone acetate in metastatic castration-resistant prostate cancer. Choudhury, AD., Gray, KP., Supko, JG., et al.[2023]

Recent advancements in treating castration-resistant prostate carcinoma include the approval of four new agents—abiraterone, cabazitaxel, enzalutamide, and radium-223 dichloride—that have been shown to improve overall survival for patients.

Cabozantinib, a targeted therapy that inhibits MET and VEGFR-2, has demonstrated promising results in clinical trials and may become a key treatment option for this type of prostate cancer, although further research is needed to determine its optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: a novel agent with a dual mechanism of action for castration-resistant prostate carcinoma. Pinto, A.[2014]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

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 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 significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., 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]

Cabozantinib, which inhibits MET and VEGFR2 signaling, has shown clinical benefits in early trials for men with metastatic prostate cancer, indicating its potential as an effective treatment option.

Preclinical studies suggest that cabozantinib not only targets cancer cells directly but also disrupts the supportive environment (angiogenesis and stromal cells) that allows metastasis to thrive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib and prostate cancer: inhibiting seed and disrupting soil? Lee, RJ., Smith, MR.[2021]

References

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

Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). [2022]

2. England pubmed.ncbi.nlm.nih.gov

A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib. [2021]

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

A dose finding clinical trial of cabozantinib (XL184) administered in combination with abiraterone acetate in metastatic castration-resistant prostate cancer. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Cabozantinib: a novel agent with a dual mechanism of action for castration-resistant prostate carcinoma. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

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

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

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

Atezolizumab: First Global Approval. [2019]

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

Cabozantinib and prostate cancer: inhibiting seed and disrupting soil? [2021]