Cabozantinib + Abiraterone + Immunotherapy for Prostate Cancer

Overseen By Melissa A Reimers, M.D.

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must be taking: Androgen deprivation therapy

Must not be taking: CYP3A4 inducers/inhibitors, Anticoagulants

Disqualifiers: Neuroendocrine cancer, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 24 months

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to determine the recommended phase 2 dose of the multi-drug combination of abiraterone, cabozantinib, and nivolumab in conjunction with ongoing androgen deprivation therapy in previously untreated metastatic hormone-sensitive prostate cancer patients. The investigators hypothesize that the combination of cabozantinib and abiraterone acetate/prednisone in conjunction with nivolumab will have an acceptable safety profile and will be feasible to administer in patients with hormone-sensitive metastatic prostate cancer.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot take strong CYP3A4 inducers or inhibitors. If you are on these, they must be stopped safely before joining. You must also avoid certain anticoagulants and immunosuppressive medications.

What data supports the effectiveness of the drug combination Cabozantinib, Abiraterone, and Nivolumab for prostate cancer?

Research shows that Abiraterone can improve survival in prostate cancer, but resistance can limit its effectiveness. Combining it with Cabozantinib, which has immunomodulatory properties, may enhance its anti-cancer activity. Additionally, immune checkpoint inhibitors like Nivolumab may benefit certain patients, although careful selection is needed to identify those who might respond well. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Abiraterone safe for prostate cancer treatment?

Cabozantinib and Abiraterone have been studied together in prostate cancer, and while the focus was on finding the right dose, the combination has been used in clinical settings. Abiraterone is generally used with prednisone to treat prostate cancer, and Cabozantinib has been tested with other drugs like atezolizumab, showing it is used in various combinations for prostate cancer treatment. ^{1 6 7 8 9}

What makes the drug combination of Cabozantinib, Abiraterone, and Nivolumab unique for prostate cancer?

This drug combination is unique because it combines Cabozantinib, which targets specific proteins involved in cancer growth, with Abiraterone, a hormone therapy, and Nivolumab, an immunotherapy. This multi-faceted approach aims to overcome resistance to standard treatments and enhance the overall effectiveness against prostate cancer. ^{1 5 6 10 11}

Research Team

Russell Pachynski, MD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with hormone-sensitive prostate cancer that has spread, who haven't had chemotherapy or immunotherapy before. They should be on hormone therapy for no more than 12 weeks and agree to use contraception. Excluded are those with certain types of prostate cancer, prior treatments like cabozantinib, ongoing severe illnesses, active infections like hepatitis B/C or HIV, recent surgeries, or known brain metastases.

Inclusion Criteria

My scans show cancer has spread to other parts of my body.

Your white blood cell count needs to be at least 2,500 K/cumm.

My cancer has returned or spread to other parts after initial treatment.

Exclusion Criteria

I have been treated with cabozantinib before.

I have been treated with advanced prostate cancer medications like enzalutamide.

I do not have any other cancer that needs treatment right now.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of abiraterone, cabozantinib, and nivolumab in conjunction with androgen deprivation therapy

Up to 24 months

Nivolumab is administered intravenously on Day 1 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Abiraterone acetate
• Cabozantinib
• Nivolumab

Trial Overview The CABIOS Trial is testing a combination of drugs (cabozantinib and abiraterone acetate/prednisone) alongside nivolumab in patients continuing androgen deprivation therapy. The aim is to find the safest dose for phase 2 trials while assessing if this regimen can be safely given to men with advanced prostate cancer.

Participant Groups

Group I: Level 2: Cabozantinib+Abiraterone acetate +Nivolumab Experimental Treatment 5 Interventions

-Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be 40 mg. Participants can continue to receive treatment for up to 2 years.

Group II: Level 1: Cabozantinib+Abiraterone acetate +Nivolumab Experimental Treatment 5 Interventions

-Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be 20 mg. Participants can continue to receive treatment for up to 2 years.

Group III: Expansion: Cabozantinib+Abiraterone acetate +Nivolumab Experimental Treatment 5 Interventions

-Abiraterone acetate is an oral medication given at a dose of 1000 mg daily. Prednisone is an oral medication given at a dose of 5 mg daily. Nivolumab is given intravenously over 30 minutes on Day 1 of each 28-day cycle at a dose of 480 mg. Cabozantinib is an oral drug given daily; dosing will be dependent on recommended dose found in first part of study. Participants can continue to receive treatment for up to 2 years.

Abiraterone acetate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• High-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

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

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]

The IMbassador250 trial involving 759 men with metastatic castration-resistant prostate cancer found that adding atezolizumab to enzalutamide did not improve overall survival, although it had an acceptable safety profile.

However, patients with high levels of PD-L1 expression and certain immune gene signatures showed longer progression-free survival, suggesting that careful patient selection could enhance the effectiveness of immune checkpoint inhibitors in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Powles, T., Yuen, KC., Gillessen, S., et al.[2023]

New hormonal therapies like abiraterone and enzalutamide have significantly changed the treatment landscape for metastatic castration-resistant prostate cancer, offering new options for patients.

With multiple new treatments in trials targeting various pathways, there is an urgent need to identify predictive markers to guide treatment sequencing and optimize patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New therapies in metastatic castration resistant prostate cancer]. Thibault, C., Massard, C.[2015]

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]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

In a study of 54 metastatic castration-resistant prostate cancer patients, cabazitaxel showed a PSA reduction rate of over 50% in 46.2% of patients, with a disease control rate of 83.3% after 3 months, although it had significant side effects like neutropenia in 40% of patients.

Abiraterone resulted in a PSA reduction rate of 35.1% and a disease control rate of 47.1%, with lower rates of severe hematotoxicities but higher rates of fatigue and other non-hematological side effects, indicating both treatments are effective with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Compassionate use of abiraterone and cabazitaxel: first experiences in docetaxel-pretreated castration-resistant prostate cancer patients]. Heck, MM., Höppner, M., Horn, T., et al.[2021]

Cabazitaxel, abiraterone, and enzalutamide show comparable overall survival outcomes for patients with metastatic castrate-resistant prostate cancer, with no significant differences found in median survival rates among the treatments.

However, cabazitaxel is associated with a higher risk of certain adverse events, such as anemia, diarrhea, and pyrexia, compared to abiraterone and enzalutamide, indicating a need for careful consideration of side effects when choosing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of cabazitaxel for patients with metastatic castrate-resistant prostate cancer who have been previously treated with a docetaxel-containing regimen. Fryzek, JP., Reichert, H., Summers, N., et al.[2021]

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]

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]

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

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Taxane-based chemohormonal therapy for metastatic hormone-sensitive prostate cancer. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[New therapies in metastatic castration resistant prostate cancer]. [2015]

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

Cabozantinib Inhibits Abiraterone's Upregulation of IGFIR Phosphorylation and Enhances Its Anti-Prostate Cancer Activity. [2020]

6. 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]

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

[Compassionate use of abiraterone and cabazitaxel: first experiences in docetaxel-pretreated castration-resistant prostate cancer patients]. [2021]

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

Indirect treatment comparison of cabazitaxel for patients with metastatic castrate-resistant prostate cancer who have been previously treated with a docetaxel-containing regimen. [2021]

10. 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]

11. Germany pubmed.ncbi.nlm.nih.gov

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