Cabozantinib + Atezolizumab for Prostate Cancer

(CONTACT-02 Trial)

Recruiting at 312 trial locations

Overseen By Exelixis Clinical Trials

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Exelixis

Must be taking: NHT

Must not be taking: Androgen-receptor inhibitors

Disqualifiers: Brain metastases, Spinal cord compression, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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 months

575 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 3, multi-center, randomized, open-label, controlled study designed to evaluate the safety and efficacy of cabozantinib given in combination with atezolizumab versus a second novel hormonal therapy (NHT) in men with metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with one, and only one, NHT for their prostate cancer disease.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before joining. You must stop taking abiraterone at least 1 week, cyproterone 10 days, and other androgen-receptor inhibitors like enzalutamide 2 weeks before starting the trial.

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 has been effective in early trials by targeting cancer cells and disrupting their supportive environment, which may enhance the response to immune therapies like Atezolizumab. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Atezolizumab safe for humans?

Cabozantinib and Atezolizumab have been studied together in clinical trials for prostate cancer, and while they show promise, they can cause side effects. Common side effects of Cabozantinib include fatigue, diarrhea, and high blood pressure, while Atezolizumab can cause immune-related side effects like skin rash and inflammation of organs. It's important to discuss potential risks with your doctor. ^{3 4 5 6 7}

How is the drug combination of cabozantinib and atezolizumab unique for prostate cancer?

This drug combination is unique because cabozantinib, which blocks certain proteins that help cancer cells grow, is used with atezolizumab, an immune therapy that helps the body's immune system attack cancer cells. This combination is being tested for prostate cancer that has not responded to other hormone treatments, offering a new option for patients with limited choices. ^{2 3 4 5 8}

Eligibility Criteria

Men with advanced prostate cancer that has resisted castration and have already tried one hormonal therapy can join. They must be adults with good organ function, able to follow the study plan, and not have other active cancers or severe illnesses. Men who've had major surgery recently or those on certain medications are excluded.

Inclusion Criteria

Understanding and ability to comply with protocol requirements

I have cancer that has spread outside my pelvis and can be measured.

I am fully active or can carry out light work.

Exclusion Criteria

Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per ECG within 21 days before randomization

I haven't taken any prostate cancer hormone treatments recently.

I haven't taken high-dose steroids or immunosuppressants in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib in combination with atezolizumab or a second NHT

21 months

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 months

Treatment Details

Interventions

• Atezolizumab
• Cabozantinib

Trial Overview The trial is testing Cabozantinib combined with Atezolizumab against a second novel hormonal therapy (NHT) in men whose prostate cancer has spread despite castration. It's a Phase 3 study where participants are randomly assigned to either treatment group.

Participant Groups

Group I: Experimental Arm Experimental Treatment 2 Interventions

Subjects with mCRPC will receive cabozantinib 40mg oral, qd + atezolizumab 1200mg infusion, q3w

Group II: Control Arm Active Control 3 Interventions

Subjects with mCRPC will receive active comparator of EITHER abiraterone 1000mg oral, qd + prednisone 5 mg oral, bid; OR enzalutamide 160mg oral, qd as designated by the Investigator prior to randomization

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?

Exelixis

Lead 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

Takeda

Industry Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Roche-Genentech

Industry Sponsor

Trials

27

Recruited

3,800+

Findings from Research

Combining atezolizumab, an anti-PD-L1 immunotherapy, with enzalutamide, an androgen receptor antagonist, did not improve survival rates in patients with metastatic prostate cancer.

Further research is needed to understand the mechanisms of resistance to immunotherapy in the prostate tumor microenvironment, which may help improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-L1 plus enzalutamide does not improve overall survival in prostate cancer. Siddiqui, BA., Subudhi, SK., Sharma, P.[2023]

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]

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]

Cabozantinib is an oral multitargeted tyrosine kinase inhibitor approved for advanced renal cell carcinoma and progressive metastatic medullary thyroid cancer, showing potential advantages over single-receptor TKIs.

The article reviews clinical trial data and management strategies for common adverse events associated with cabozantinib, highlighting its expanding use in treating various cancers such as prostate, hepatocellular, and lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. Markowitz, JN., Fancher, KM.[2019]

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]

References

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

Anti-PD-L1 plus enzalutamide does not improve overall survival in prostate cancer. [2023]

2. 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]

3. 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]

4. 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]

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

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

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

Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

8. 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]