Cabozantinib + Abiraterone + Immunotherapy for Prostate Cancer

No longer recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to determine their safety for treating prostate cancer that has spread and still responds to hormone therapy. The study involves three medications: abiraterone (a hormone therapy), cabozantinib (a targeted therapy), and nivolumab (an immunotherapy), administered alongside current hormone treatments. The trial aims to identify the best dose for future studies and seeks participants diagnosed with prostate cancer that has spread and have been on hormone therapy for less than 12 weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

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

Research shows that the combination of cabozantinib, abiraterone, and nivolumab is under evaluation for safety in treating prostate cancer. Previous studies with cabozantinib and nivolumab indicate that these drugs can be used safely together, with manageable side effects such as tiredness, diarrhea, and high blood pressure.

Abiraterone, when taken with prednisone, has already received approval for prostate cancer treatment and is generally well-tolerated, though it may cause joint pain and high blood pressure.

This trial is in its early stages, with researchers still determining the best dosages and closely monitoring safety. So far, these treatments are considered safe enough for continued study in people. Participants should discuss any concerns with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cabozantinib, Abiraterone acetate, and Nivolumab for treating prostate cancer because it offers a unique multi-faceted approach. Unlike standard treatments that typically focus on one mechanism, this combination targets cancer in three ways. Cabozantinib inhibits tumor growth and spread by targeting specific proteins in cancer cells, Abiraterone acetate reduces androgen levels that fuel cancer growth, and Nivolumab boosts the immune system to better attack cancer cells. This triple threat aims to not only halt cancer progression but also enhance the body's natural defenses, potentially offering a more comprehensive treatment option.

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

This trial will evaluate the combination of cabozantinib, abiraterone, and nivolumab for treating metastatic hormone-sensitive prostate cancer. Research has shown that using these three drugs together may help treat this condition. Studies have found that cabozantinib, when combined with other treatments, can extend the time during which the cancer does not worsen. Abiraterone is known to help treat prostate cancer by blocking testosterone, which slows cancer growth. Nivolumab is an immunotherapy that enhances the immune system's ability to attack cancer cells. Early trials with these three drugs together showed promising results, suggesting they may work well as a combination. Participants in this trial will receive different dosing levels of cabozantinib alongside abiraterone and nivolumab to determine the most effective regimen. ^{1 2 4 5 6}

Who Is on the Research Team?

Russell Pachynski, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.186

A phase 1b study of cabozantinib and nivolumab with ... Conclusions: Here, we present updated clinical and immune correlative findings of the first trial of cabozantinib in combination with nivolumab ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04477512?id=%22NCT01428219%22OR%22NCT01574937%22OR%22NCT01630590%22OR%22NCT01834651%22OR%22NCT03964337%22OR%22NCT04477512%22OR%22NCT04631744%22&rank=2

Study Details | NCT04477512 | Cabozantinib and ... 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 ...

3. urotoday.com urotoday.com/conference-highlights/asco-2023/asco-2023-prostate-cancer/144842-asco-2023-cabios-trial-a-phase-ib-study-of-cabozantinib-and-nivolumab-in-combination-with-abiraterone-in-patients-with-metastatic-hormone-sensitive-prostate-cancer.html

CABIOS Trial: A Phase Ib Study of Cabozantinib and ... Dr. Jesse Zaretsky presented the results of CABIOS, a phase Ib study of cabozantinib and nivolumab in combination with abiraterone in patients with metastatic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9340935/

Cabozantinib combination therapy for the treatment of solid ... This review demonstrates the promising efficacy outcomes of cabozantinib combined with other therapies, and a safety profile similar to cabozantinib alone.

5. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00209-8/abstract

Cabozantinib plus atezolizumab in metastatic prostate ... After a median follow-up of 11·8 months (IQR 9·9–19·3), cabozantinib plus atezolizumab significantly improved progression-free survival versus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6286224/

A dose finding clinical trial of cabozantinib (XL184 ... Cabozantinib can enhance the effect of abiraterone in preclinical prostate cancer models. This study aimed to define the recommended phase 2 dose (RP2D) and ...