Atezolizumab-Based Combination Therapy for Prostate Cancer

Recruiting at 2 trial locations

Overseen By Lawrence Fong

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: David Oh

Must not be taking: Antiandrogens, Chemotherapy, Immunotherapy, others

Disqualifiers: Metastatic disease, Autoimmune disease, Cardiovascular, 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: 6

Duration: 2 weeks

68 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications. However, if you are on finasteride or dutasteride, you must stop and have a 6-week washout period before joining. Also, if you are on certain medications like strong CYP3A4 inducers or inhibitors, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications. If you are on finasteride or dutasteride, you must stop and have a 6-week period without these medications before joining the study. Other medications may also need to be stopped, but the protocol does not specify all of them.

What data supports the idea that Atezolizumab-Based Combination Therapy for Prostate Cancer is an effective treatment?

The available research shows mixed results for Atezolizumab-Based Combination Therapy in treating prostate cancer. One study found that adding atezolizumab to enzalutamide did not improve survival in patients with metastatic prostate cancer. However, another study indicated that combining cabozantinib with atezolizumab showed promising results for patients with metastatic castration-resistant prostate cancer, especially those who had limited options after other treatments. This suggests that while the therapy may not be effective for all patients, it could be beneficial for certain groups, particularly when combined with other drugs like cabozantinib. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Atezolizumab for prostate cancer?

Some studies suggest that Atezolizumab, when combined with other treatments like cabozantinib, may show promising results for certain patients with advanced prostate cancer. However, its effectiveness as a standalone treatment or in combination with enzalutamide has not significantly improved overall survival in broader patient groups. ^{1 2 3 4 5}

What safety data is available for Atezolizumab-based therapy?

Atezolizumab, also known as Tecentriq, has been evaluated for safety in various clinical trials. It has been approved by the FDA for use in urothelial carcinoma and non-small cell lung cancer. The toxicity profile of Atezolizumab is considered favorable, with manageable safety in patients with advanced bladder cancer and non-small-cell lung cancer. In trials, treatment-related toxicities were reported in 66% of patients, with 7-12% experiencing grade 3-4 adverse events. Overall, Atezolizumab has shown a manageable safety profile in patients with metastatic urothelial carcinoma and other cancers. ^{6 7 8 9 10}

Is Atezolizumab-based therapy generally safe for humans?

Atezolizumab, also known as Tecentriq, has been shown to have a favorable safety profile in studies for bladder and lung cancer, with manageable side effects. Most treatment-related side effects were mild, but some patients experienced more severe reactions. ^{6 7 8 9 10}

Is the drug Atezolizumab, Etrumadenant, Tocilizumab a promising treatment for prostate cancer?

Atezolizumab, known as Tecentriq, is a drug that has shown promise in treating various cancers by boosting the body's immune response against tumors. It has been approved for use in bladder and lung cancers, and studies suggest it could be effective when combined with other treatments. This makes it a promising option for further research in treating prostate cancer. ^{6 7 8 9 11}

What makes the drug Atezolizumab-based combination therapy unique for prostate cancer?

Atezolizumab-based combination therapy is unique because it combines Atezolizumab, a drug that boosts the immune system by blocking a protein called PD-L1, with other agents like Etrumadenant and Tocilizumab, potentially enhancing its effectiveness against prostate cancer. This combination aims to improve immune response and target cancer cells more effectively than using Atezolizumab alone. ^{6 7 8 9 11}

What is the purpose of this trial?

This phase II trial studies how well atezolizumab works alone or in combination with etrumadenant or tocilizumab in treating men with localized prostate cancer before radical prostatectomy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Androgens can cause the growth of prostate cancer cells. IL-6 is expressed by prostate cancer and within the tumor microenvironment and shown to enhance prostate cancer and disease progression. Treatment with an anti-IL-6 antibody such as tocilizumab may inhibit cancer progression. Giving atezolizumab in combination with etrumadenant or tocilizumab may work better in treating prostate cancer.

Research Team

David Y Oh, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Men with localized prostate cancer who haven't had previous treatments for it, are over 18, in good health with proper organ and marrow function, and eligible for surgery. They must have high-risk disease for certain parts of the trial, a testosterone level above 150 ng/dL, agree to use contraception and not donate sperm.

Inclusion Criteria

You need to have a tumor sample that is suitable for the study analysis, as determined by the study leader.

Contraception: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Testosterone level > 150 ng/dL

Exclusion Criteria

I haven't taken any immune-boosting drugs in the last 4 weeks.

This does not apply to me as it is an exclusion criterion.

I have previously been treated with specific immune therapies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one cycle of atezolizumab-based combination therapy prior to radical prostatectomy

2 weeks

1 visit (in-person)

Radical Prostatectomy

Radical prostatectomy occurs 21 days (+/- 7 days) following the final dose of atezolizumab

3-4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

4 visits (in-person) at 6 weeks, 3 months, 6 months, and 12 months

Treatment Details

Interventions

• Atezolizumab
• Etrumadenant
• Tocilizumab

Trial Overview The effectiveness of Atezolizumab alone or combined with Etrumadenant or Tocilizumab is being tested before surgical removal of the prostate. The study aims to see if these treatments can help the immune system fight cancer better than current methods.

Participant Groups

Group I: Cohort C (atezolizumab, tocilizumab) Experimental Treatment 2 Interventions

Participants will receive one (1) cycle of neoadjuvant atezolizumab and one (1) cycle of tocilizumab, 6mg/kg will be administered IV on day 1 of a 14 day IV prior to RP; atezolizumab will be administered in an identical fashion as Cohort A. RP will occur 21 days (+/- 7 days) following the final dose of atezolizumab. No further study therapy will be administered following RP.

Group II: Cohort B (atezolizumab, etrumadenant) Experimental Treatment 2 Interventions

Participants will receive one (1) cycle of atezolizumab, 1200mg intravenously (IV) over 30-60 minutes on day 1 of a 14 day cycle and etrumadenant will be taken at a dose of 150mg PO, once daily, until 48 hours prior to RP, for at least 12 days. Radical Prostatectomy (RP) will occur 21 days (+/- 7 days) following the final dose of atezolizumab. No further study therapy will be administered following RP.

Group III: Cohort A (atezolizumab monotherapy) Experimental Treatment 1 Intervention

Participants receive one (1) cycle of atezolizumab, 1200mg intravenously (IV) over 30-60 minutes on day 1 of a 14 day cycle. Radical Prostatectomy (RP) will occur 21 days (+/- 7 days) following the final dose of atezolizumab. No further study therapy will be administered following RP.

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?

David Oh

Lead Sponsor

Trials

2

Recruited

50+

Lawrence Fong

Lead Sponsor

Trials

6

Recruited

90+

Arcus Biosciences, Inc.

Industry Sponsor

Trials

44

Recruited

7,500+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

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 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]

Atezolizumab, an anti-PD-L1 therapy, was generally well tolerated in 35 patients with metastatic castration-resistant prostate cancer (mCRPC), showing a safety profile similar to that observed in other cancers, with no treatment-related deaths.

While there was some evidence of disease control, with a median overall survival of 14.7 months, the efficacy was limited, indicating that atezolizumab may be more effective when used in combination with other treatments rather than as a monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase I Study. Petrylak, DP., Loriot, Y., Shaffer, DR., 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]

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]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

Atezolizumab, a monoclonal antibody targeting PD-L1, shows promising efficacy in treating metastatic colorectal cancer (mCRC), particularly in patients with deficient mismatch repair (dMMR), indicating a potential new treatment avenue for this subgroup.

Ongoing clinical trials suggest that atezolizumab may be even more effective when combined with chemotherapy or targeted therapies, such as the MEK inhibitor cobimetinib, paving the way for its inclusion in future treatment protocols for mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. Tapia Rico, G., Price, TJ.[2022]

References

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

Anti-PD-L1 plus enzalutamide does not improve overall survival in 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. United States pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase I Study. [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. 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]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. [2022]