Cabozantinib + Nivolumab for Advanced Prostate Cancer

(CANOPY Trial)

Recruiting at3 trial locations

Overseen by Rana R. McKay, MD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Rana McKay, MD

Must be taking: AR-targeting agents

Must not be taking: Checkpoint inhibitors, Cabozantinib

Disqualifiers: Autoimmune disease, Brain metastases, Hepatitis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a multicenter, single-arm, two-stage open-label phase 2 study of the combination of cabozantinib + nivolumab in subjects with advanced castration-resistant prostate cancer (CRPC).

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting the study treatment. Specifically, you must stop taking any small molecule kinase inhibitors 2 weeks before, and any cytotoxic, biologic, or investigational systemic anti-cancer agents 4 weeks before the first dose. Additionally, certain prostate cancer treatments like abiraterone, apalutamide, or darolutamide must be stopped 2 weeks before, and enzalutamide 4 weeks before treatment initiation.

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

Research shows that Cabozantinib, when combined with another immune drug, has shown promising results in treating advanced prostate cancer. Additionally, Cabozantinib has been effective in improving progression-free survival in prostate cancer, suggesting potential benefits when used with immune drugs like Nivolumab. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Nivolumab safe for humans?

The combination of Cabozantinib and Nivolumab has been studied for safety in patients with advanced renal cell carcinoma. The safety profile is generally manageable with strategies like dose adjustments and supportive care to handle side effects such as diarrhea, fatigue, and skin reactions. ^{2 3 6 7 8}

How is the drug combination of Cabozantinib and Nivolumab unique for advanced prostate cancer?

The combination of Cabozantinib and Nivolumab is unique because Cabozantinib targets multiple pathways involved in cancer growth and spread, while Nivolumab helps the immune system recognize and attack cancer cells. This dual approach may offer a new option for patients with advanced prostate cancer who have limited treatment choices after hormonal therapies. ^{1 2 3 9 10}

Research Team

Rana R. McKay, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

Men over 18 with advanced prostate cancer that's resistant to hormone therapy can join this trial. They must have tried one chemo drug and one hormone-targeting treatment, be willing to use birth control, and have their disease getting worse. HIV-positive men are eligible if treated and stable. People can't join if they've had certain other treatments recently or have specific health issues like severe lung conditions or brain metastases.

Inclusion Criteria

My prostate cancer has been confirmed by lab tests.

I am a man aged 18 or older.

Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.

Exclusion Criteria

I have a condition that prevents my body from absorbing nutrients properly.

My brain metastases have been treated and stable for at least 4 weeks.

Other clinically significant disorders that would preclude safe study participation.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib (40 mg orally daily) and nivolumab (480 mg intravenously every four weeks) until radiographic progression, toxicity, or withdrawal

Up to 3 years

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Cabozantinib (Tyrosine Kinase Inhibitor)
• Nivolumab (Checkpoint Inhibitor)

Trial Overview The study is testing a combination of two drugs, Cabozantinib and Nivolumab, in men with metastatic castration-resistant prostate cancer (CRPC). It's an open-label phase 2 trial where all participants receive the same treatment without being compared to a placebo or another drug.

Participant Groups

Group I: Experimental Group Experimental Treatment 2 Interventions

40 mg of cabozantinib taken orally every day (days 1-28) of a 28 day cycle 480 mg of nivolumab given intravenously on the first day (day 1) of each 28 day cycle

Cabozantinib is already approved in Canada, Japan for the following indications:

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

Rana McKay, MD

Lead Sponsor

Trials

2

Recruited

80+

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

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

Findings from Research

In a study of 62 patients with hormone-naïve metastatic prostate cancer, cabozantinib combined with androgen deprivation therapy (ADT) showed a median progression-free survival (mPFS) of 16.1 months, indicating promising efficacy in delaying disease progression.

The treatment resulted in significant reductions in prostate-specific antigen (PSA) and other biomarkers in a high percentage of patients, although 85% experienced dose reductions due to adverse events, primarily hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Cabozantinib and Androgen Ablation in Patients with Hormone-Naïve Metastatic Prostate Cancer. Corn, PG., Zhang, M., Nogueras-Gonzalez, GM., 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]

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]

In a study of 326 prostate adenocarcinoma patients from Spain and Norway, high expression of the immune checkpoint protein B7-H3 was linked to worse outcomes, including biochemical and clinical recurrence, indicating its potential as a target for immunotherapy.

Unlike B7-H3, PD-L1 expression did not show a correlation with clinical outcomes, suggesting that B7-H3 may be a more relevant biomarker for treatment strategies in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer. Nunes-Xavier, CE., Kildal, W., Kleppe, A., et al.[2022]

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]

Cabazitaxel is a potentially effective treatment for castration-resistant prostate cancer (CRPC) in patients aged 80 years and older, showing similar efficacy in overall survival and PSA response rates compared to younger patients.

The safety profile of cabazitaxel is comparable across age groups, with high rates of adverse drug reactions (ADRs) in both patients aged <80 (77.2%) and ≥80 years (79.6%), primarily involving hematologic toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel in patients aged ≥80 years with castration-resistant prostate cancer: Results of a post-marketing surveillance study in Japan. Matsubara, N., Suzuki, K., Kazama, H., et al.[2021]

The combination of cabozantinib (a tyrosine kinase inhibitor) and nivolumab (an immune checkpoint inhibitor) significantly improved progression-free survival, overall survival, and objective response rates in patients with untreated advanced renal cell carcinoma compared to sunitinib, supporting its approval as a first-line therapy.

While the safety profile of the combination treatment is generally manageable, it requires careful monitoring and management of overlapping adverse events, such as diarrhea and hepatotoxicity, to maintain patient tolerability and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. McGregor, B., Mortazavi, A., Cordes, L., et al.[2023]

In a phase II study involving 144 patients with castration-resistant prostate cancer, cabozantinib demonstrated significant efficacy, with 63% of patients showing a bone scan response and 57% experiencing meaningful pain relief.

Cabozantinib was associated with improvements in various clinical outcomes, including reductions in narcotic use and measurable soft tissue disease, while the most common severe side effects were fatigue and hypertension, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib in chemotherapy-pretreated metastatic castration-resistant prostate cancer: results of a phase II nonrandomized expansion study. Smith, MR., Sweeney, CJ., Corn, PG., et al.[2021]

In a study of 25 men with metastatic castration-resistant prostate cancer (mCRPC), cabozantinib demonstrated significant efficacy, with 77% of patients achieving stable disease or better after 12 weeks, and a median progression-free survival of 43.7 weeks.

Cabozantinib led to notable changes in bone scans for 36% of patients, indicating its potential to improve bone health in mCRPC, alongside changes in biomarkers related to bone formation and the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer. Smith, DC., Daignault-Newton, S., Grivas, P., et al.[2022]

References

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

A Phase II Study of Cabozantinib and Androgen Ablation in Patients with Hormone-Naïve Metastatic Prostate Cancer. [2023]

2. 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]

3. 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]

4. 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]

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

Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer. [2022]

6. United States 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. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Cabazitaxel in patients aged ≥80 years with castration-resistant prostate cancer: Results of a post-marketing surveillance study in Japan. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. [2023]

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

Cabozantinib in chemotherapy-pretreated metastatic castration-resistant prostate cancer: results of a phase II nonrandomized expansion study. [2021]

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

Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer. [2022]