Cabozantinib + Atezolizumab for Prostate Cancer

(CONTACT-02 Trial)

Not currently recruiting at 380 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, cabozantinib (Cabometyx) and atezolizumab (Tecentriq), for treating advanced prostate cancer that has spread beyond the prostate and resists hormone therapy. Researchers aim to determine if this combination is more effective than other hormone treatments. Men with prostate cancer that continues to grow despite previous hormone therapy might be suitable candidates. Participants must have undergone only one prior hormone treatment and must show signs of cancer progression. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that patients generally tolerate the combination of cabozantinib and atezolizumab well. Previous studies found that most people do not experience severe side effects. Importantly, no new safety concerns have emerged, suggesting the treatment is relatively safe based on current data. While some side effects may occur, they resemble those previously seen with these drugs and are considered manageable by healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cabozantinib and atezolizumab for prostate cancer because it offers a novel approach compared to standard treatments like abiraterone or enzalutamide. Most treatments for metastatic castration-resistant prostate cancer (mCRPC) focus on hormone pathways, but cabozantinib targets multiple tyrosine kinases involved in tumor growth and angiogenesis, which could effectively cut off the tumor's blood supply. Atezolizumab, on the other hand, is an immunotherapy that helps the immune system recognize and attack cancer cells. This dual approach not only targets the cancer directly but also harnesses the body's immune defenses, potentially leading to improved outcomes for patients.

What evidence suggests that cabozantinib and atezolizumab could be effective for metastatic castration-resistant prostate cancer?

This trial will compare the combination of cabozantinib and atezolizumab with other treatments for advanced prostate cancer that no longer responds to hormone therapy. Research has shown that cabozantinib with atezolizumab may help treat this condition, as studies have found that this combination can effectively attack and destroy cancer cells. Clinical evidence suggests that this treatment can extend patients' lives compared to other treatments. Patients whose cancer has spread beyond the prostate have shown particular benefits. This combination is also considered safe, with no new safety issues reported. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

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

Cabozantinib plus atezolizumab in metastatic prostate ... Treatment patterns and outcomes in patients with metastatic castration-resistant prostate cancer in a real-world clinical practice setting in the United States

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40523369/

final analyses from a phase 3, open-label, randomised trial We aimed to assess efficacy and safety of cabozantinib, a tyrosine kinase inhibitor with immunomodulatory properties, plus the PD-L1 inhibitor ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.145

Cabozantinib (C) ± atezolizumab (A) in patients (pts) with ... C and C+A demonstrated clinical activity in pts with mCRPC and extrapelvic soft tissue mets, with no new safety signals.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05168618

NCT05168618 | Cabozantinib and Atezolizumab for the ... Giving cabozantinib and atezolizumab may kill more tumor cells in patients with metastatic castrate-resistant prostate cancer. Detailed Description. PRIMARY ...

5. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-prostate-cancer/154863-esmo-2024-cabozantinib-plus-atezolizumab-versus-2nd-novel-hormonal-therapy-in-patients-with-metastatic-castration-resistant-prostate-cancer-final-overall-survival-results-of-the-phase-iii-randomized-contact-02-study.html

ESMO 2024: Cabozantinib plus Atezolizumab versus 2nd ... Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04446117

NCT04446117 | Study of Cabozantinib in Combination ... This is a Phase 3, multi-center, randomized, open-label, controlled study designed to evaluate the safety and efficacy of cabozantinib given in combination ...

7. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-detailed-results-phase-3-contact-02-pivotal

Exelixis Announces Detailed Results of Phase 3 CONTACT ... Cabozantinib in combination with atezolizumab reduced the risk of disease progression or death by 35% in patients with metastatic castration-resistant prostate ...

8. urotoday.com urotoday.com/conference-highlights/esmo-2021/esmo-2021-prostate-cancer/132207-esmo-2021-lba24-cabozantinib-c-in-combination-with-atezolizumab-a-in-patients-pts-with-metastatic-castration-resistant-prostate-cancer-mcrpc-results-of-expanded-cohort-6-of-the-cosmic-021-study.html

Results of Expanded Cohort 6 of the COSMIC-021 Study These data from Cohort 6 of COSMIC-021 demonstrate that cabozantinib + atezolizumab has clinically meaningful activity with a manageable safety profile in ...