Atezolizumab-Based Combination Therapy for Prostate Cancer

Recruiting at 3 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of atezolizumab alone or in combination with other drugs in treating prostate cancer before surgery. Atezolizumab, a type of immunotherapy, helps the immune system attack cancer cells. The trial will test atezolizumab by itself and with etrumadenant (an experimental treatment) or tocilizumab, which may help slow cancer growth. This trial targets men with localized prostate cancer who plan to undergo surgery and have not received other prostate cancer treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that atezolizumab, when used alone, is generally well tolerated. Studies have found that patients with advanced prostate cancer managed the treatment well, experiencing side effects similar to those in other cancer types. Common side effects might include tiredness and nausea, but these are often manageable.

For the combination of atezolizumab and etrumadenant, specific data remains limited. However, atezolizumab has a known safety record, and etrumadenant has not shown any severe side effects in similar studies. This suggests that the combination might be tolerable, though more data is needed to confirm this.

Regarding the mix of atezolizumab and tocilizumab, tocilizumab is already approved for treating some inflammatory conditions, indicating a reasonable safety record. When combined with atezolizumab, the safety is expected to be acceptable, but specific data from this exact combination is not yet available.

Overall, these treatments are part of a phase 2 trial, indicating some safety in earlier studies, but researchers are still gathering detailed information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for prostate cancer, which typically involve surgery, radiation, or hormone therapy, the combination therapy involving atezolizumab is unique because it uses the immune system to fight cancer. Atezolizumab is an immunotherapy drug that helps the body's immune system recognize and attack cancer cells. Researchers are particularly excited about combining atezolizumab with etrumadenant, which targets the adenosine pathway to potentially enhance immune response, and tocilizumab, which targets interleukin-6 and may reduce inflammation. These combinations aim to improve the effectiveness and precision of treatment, offering new hope for patients with prostate cancer.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will evaluate the effects of different atezolizumab-based combination therapies for prostate cancer. Studies have shown that atezolizumab can help the body's immune system fight prostate cancer. In this trial, participants in Cohort A will receive atezolizumab monotherapy. Cohort B will receive a combination of atezolizumab and etrumadenant, which might improve results, as seen in studies with similar cancer types. Cohort C will receive atezolizumab combined with tocilizumab, which targets IL-6, a protein that can help cancer grow; blocking it might slow or stop cancer progression. These treatments aim to strengthen the immune response and slow cancer growth, offering hope for better management of prostate cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

David Y Oh, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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, 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]

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]

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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33568344/

Safety and Clinical Activity of Atezolizumab in Patients with ... Median overall survival (OS) was 14.7 months [95% confidence interval (CI): 5.9-not evaluable], with a 1-year OS rate of 52.3% (95% CI: 34-70); ...

2. 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 ...

3. renalandurologynews.com renalandurologynews.com/news/cabozantinib-atezolizumab-arpi-switching-mcrpc/

Cabozantinib Plus Atezolizumab Appears More Effective ... At a median follow-up of 11.8 months, cabozantinib plus atezolizumab improved progression-free survival (PFS). The median PFS was 6.3 months ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9406237/

a randomised phase 3 trial - PMC - PubMed Central Adding atezolizumab to enzalutamide in an open label randomised trial did not meet the primary endpoint of improved overall survival in unselected patients ( ...

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

Cabozantinib plus atezolizumab in metastatic prostate ... After a median follow-up of 11·8 months (IQR 9·9–19·3), cabozantinib plus atezolizumab significantly improved progression-free survival versus ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/27/12/3360/671439/Safety-and-Clinical-Activity-of-Atezolizumab-in

Safety and Clinical Activity of Atezolizumab in Patients with ... Prespecified endpoints included safety, efficacy, biomarker analyses, and radiographic assessments. Results: All 35 evaluable patients [median age, 68 years ( ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.6_suppl.187

A phase Ia study of safety and clinical activity ... Conclusions: Atezo was well tolerated and demonstrated long-term disease control in pts with heavily pretreated mCRPC, with a 12-mo OS rate of ...