Cabozantinib + Nivolumab for Advanced Prostate Cancer

(CANOPY Trial)

Recruiting at 3 trial locations

Overseen By Gabrielle Tiggs

Age: 18+

Sex: Male

Trial Phase: Phase 2

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 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: 1

Duration: Up to 3 years

47 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments: cabozantinib (Cabometyx, a cancer drug) and nivolumab (Opdivo, an immunotherapy drug), for advanced prostate cancer unresponsive to standard hormone therapy. The goal is to evaluate the effectiveness of these treatments in controlling cancer growth. It targets men who have tried other treatments, such as hormone therapy and chemotherapy, but still experience disease progression. Participants should have prostate cancer that grows despite low testosterone levels and have previously used certain cancer drugs. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that the combination of cabozantinib and nivolumab is likely to be safe for humans?

Research has shown that the combination of cabozantinib and nivolumab has been tested in earlier studies, primarily for various cancer types. These studies indicate that patients generally tolerate the combination well. Some experienced side effects like tiredness and nausea, but these were usually manageable.

Both cabozantinib and nivolumab have been used separately for other conditions, providing reassurance about their safety. Nivolumab is an immunotherapy that helps the body's immune system fight cancer, while cabozantinib is a targeted therapy that blocks proteins aiding cancer cell growth. Together, they aim to combat cancer more effectively.

Although earlier studies do not provide all the answers, they suggest the treatment is relatively safe. However, individual responses vary, so discussing any concerns with a healthcare professional before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cabozantinib and nivolumab for advanced prostate cancer because they offer a fresh approach compared to conventional treatments like androgen deprivation therapy and chemotherapy. Cabozantinib is unique because it targets multiple pathways involved in cancer growth and spread, potentially overcoming resistance seen in other treatments. Nivolumab, on the other hand, is an immune checkpoint inhibitor that boosts the body's own immune response against cancer cells. This combination aims to enhance effectiveness by simultaneously attacking the cancer from different angles, which could lead to improved outcomes for patients.

What evidence suggests that the combination of cabozantinib and nivolumab could be effective for advanced prostate cancer?

Research has shown that using cabozantinib and nivolumab together may help treat advanced cancers. Studies indicate that this combination works better than using either drug alone. For example, one study found that 43% of patients experienced a noticeable reduction in tumor size, with nearly half seeing significant shrinkage. In another study, this combination nearly doubled the time patients lived without their cancer worsening compared to another treatment. This trial will evaluate the effectiveness of cabozantinib plus nivolumab specifically for advanced prostate cancer, building on these promising results. ^{1 2 3 6 7}

Who Is on the Research Team?

Rana R. McKay, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib
• Nivolumab

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

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

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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]

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]

Citations

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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 ...

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Phase I Study of Cabozantinib and Nivolumab Alone or ... In patients with mUC, the efficacy was higher than previously reported for single-agent ICIs (15%-20%) or monotherapy with cabozantinib (19%), with an ORR of ...

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Exelixis Announces Phase 1 Trial Results for Cabozantinib in ... The objective response rate was 43 percent among the 23 patients who were evaluable for response, with one complete response and nine partial responses. Four of ...

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Nivolumab/Cabozantinib Demonstrates Long-Term ... Nivolumab plus cabozantinib yielded a median PFS of 16.4 months compared with 8.3 months from sunitinib alone in the first-line treatment of patients with ...

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NCT05502315 | Study of Cabozantinib and Nivolumab in ... The primary endpoint is the efficacy of treatment via assessment of 6 month rPFS defined by RECIST version 1.1 for soft tissue and Prostate Cancer Working Group ...

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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 ...

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Cabometyx® in combination with Opdivo® demonstrated ... Updated results to be presented at ASCO GU 2022 showed sustained efficacy and tumor shrinkage benefits with Cabometyx (cabozantinib) in ...