Golimumab + Apalutamide for Prostate Cancer

Overseen By Patrick Panlasigui

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: Novel hormonal therapy

Must not be taking: TNF-alpha inhibitors, DMARDS

Disqualifiers: Chemotherapy in CRPC, CNS 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

Compensation: Varies

Number of Visits: 9

Duration: 24 weeks

34 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that medications known to lower the seizure threshold must be stopped or substituted at least 4 weeks before joining the study. If you are taking such medications, you will need to discuss alternatives with your doctor.

What data supports the effectiveness of the drug combination Golimumab + Apalutamide for prostate cancer?

Research shows that Apalutamide, when added to standard hormone therapy, significantly improves survival and delays disease progression in men with certain types of prostate cancer. This suggests that Apalutamide is effective in treating prostate cancer, although specific data on the combination with Golimumab is not available. ^{1 2 3 4 5}

Is the combination of Golimumab and Apalutamide safe for humans?

Apalutamide (also known as Erleada) has been studied for prostate cancer and is generally considered safe, with no substantial safety differences compared to placebo in clinical trials. However, specific safety data for the combination of Golimumab and Apalutamide is not provided in the available research. ^{2 6 7 8 9}

How is the drug combination of Golimumab and Apalutamide unique for prostate cancer treatment?

The combination of Golimumab and Apalutamide for prostate cancer is unique because it pairs a next-generation androgen receptor inhibitor (Apalutamide) with an anti-inflammatory drug (Golimumab), which is typically used for autoimmune conditions, potentially offering a novel approach by targeting both cancer growth and inflammation. ^{2 3 6 10 11}

What is the purpose of this trial?

This phase II trial tests how well golimumab and apalutamide work in treating patients with castration resistant prostate cancer. Golimumab is in a class of medications called tumor necrosis factor (TNF) inhibitors. It works by blocking the action of TNF, a substance in the body that causes inflammation. Apalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells. Giving golimumab and apalutamide may work better in treating patients with castration-resistant prostate cancer.

Research Team

Ruben Raychaudhuri, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

Men with castration-resistant prostate cancer who have tried hormone therapy for at least 6 months and show signs of disease progression. They must be over 18, understand the study, and agree to use contraception. Excluded are those with small cell or neuroendocrine prostate cancer, recent chemotherapy in the CRPC setting, certain infections like hepatitis B/C, major surgery within two weeks before the trial or planned during it.

Inclusion Criteria

Platelet count >= 100,000 x 10^9/uL

I have been diagnosed with prostate cancer through a tissue examination.

I do not have symptoms that suggest I have tuberculosis.

Exclusion Criteria

Suicidal ideation

I have an immune deficiency or HIV.

Infected joint prosthesis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive golimumab subcutaneously every 4 weeks for 6 doses and apalutamide orally daily. Treatment with apalutamide continues in the absence of disease progression or unacceptable toxicity.

24 weeks

6 visits (in-person) for golimumab administration, daily oral intake of apalutamide

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up includes tumor biopsy, CT/MRI scans, PSMA PET, and blood sample collection.

Every 3 months

Regular visits every 3 months

Long-term follow-up

Monitoring for time to subsequent antineoplastic therapy and incidence of adverse events.

Up to 4 years

Treatment Details

Interventions

• Apalutamide
• Golimumab

Trial Overview The TRAMP study is testing golimumab (a TNF inhibitor that reduces inflammation) combined with apalutamide (an androgen receptor inhibitor that blocks male hormones) to see if they're effective against advanced prostate cancer resistant to standard hormonal treatments.

Participant Groups

Group I: Treatment (golimumab, apalutamide) Experimental Treatment 8 Interventions

Patients receive golimumab SC every 4 weeks for 6 doses and apalutamide PO daily. Treatment with apalutamide continues in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy at baseline and during cycle 4. Patients also undergo CT scans or MRI, PSMA PET, bone scan, and collection of blood samples throughout the study.

Apalutamide is already approved in United States, European Union for the following indications:

Approved in United States as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

In two randomized studies involving metastatic castration-resistant prostate cancer patients, the updated median overall survival (OS) was found to be 33.3 months for the STAMP study and 32.5 months for the STRIDE study, showing no significant difference in OS whether androgen receptor-targeting agents were given sequentially or concurrently with sipuleucel-T.

Sipuleucel-T demonstrated an enhanced immune response with increased activation of antigen-presenting cells in subsequent infusions, and no new safety concerns were identified, indicating its continued efficacy and safety in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials. Antonarakis, ES., Subudhi, SK., Pieczonka, CM., et al.[2023]

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[2021]

In the SPARTAN study, apalutamide significantly improved overall survival (OS) in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), showing a 25% reduction in the risk of death compared to placebo after a median follow-up of 41 months.

Apalutamide also enhanced second progression-free survival (PFS2) by 45%, indicating its efficacy in delaying disease progression, with no new safety concerns reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Small, EJ., Saad, F., Chowdhury, S., et al.[2023]

In a study involving 1,052 patients with metastatic castration-sensitive prostate cancer, apalutamide combined with androgen deprivation therapy (ADT) led to significant improvements in prostate-specific antigen (PSA) decline compared to placebo, with 90% of patients achieving a PSA decline of at least 50%.

The study found that achieving a deep PSA decline (≥90% or to ≤0.2 ng/ml) within 3 months of treatment with apalutamide was strongly associated with better overall survival and progression-free survival, indicating that rapid PSA response can be a predictor of long-term treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer. Chowdhury, S., Bjartell, A., Agarwal, N., et al.[2023]

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]

Apalutamide is an oral androgen receptor inhibitor that effectively blocks androgen effects, and it received its first global approval in February 2018 for treating non-metastatic castration-resistant prostate cancer (nmCRPC).

Currently, apalutamide is being tested in phase III trials for various prostate cancer stages, including metastatic castration-resistant prostate cancer and high-risk localized prostate cancer, indicating its potential for broader applications in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. Al-Salama, ZT.[2019]

Men with advanced prostate cancer taking abiraterone have a significantly higher risk of major metabolic or cardiovascular adverse events compared to those not on the medication, with a hazard ratio of 1.77.

Enzalutamide also increases the risk of major adverse events, but to a lesser extent (hazard ratio of 1.22), and does not significantly increase the risk of minor adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. Lai, LY., Oerline, MK., Caram, MEV., et al.[2023]

In a review of seven randomized controlled trials involving 7103 patients with castration-resistant prostate cancer, abiraterone was found to significantly increase the risk of both any grade (RR = 1.34) and severe grade (RR = 1.71) cardiac disorders.

Enzalutamide was associated with a much higher risk of developing any grade (RR = 2.66) and severe grade (RR = 2.79) hypertension, indicating that while both drugs have cardiovascular risks, they affect different aspects of heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: a systematic review with pairwise and network meta-analyses. Lee, HY., Chen, HL., Teoh, JY., et al.[2022]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

In the SPARTAN trial, apalutamide significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen-deprivation therapy, demonstrating its efficacy as a treatment option.

Apalutamide was generally well tolerated, with fatigue being the most common side effect, indicating a favorable safety profile while maintaining health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Al-Salama, ZT.[2020]

Apalutamide, when used in combination with androgen deprivation therapy (ADT), significantly improves overall survival in patients with advanced prostate cancer, as demonstrated in two phase 3 clinical trials (SPARTAN and TITAN).

The treatment is well tolerated across a diverse patient population, including those with varying risk levels of metastatic disease, and its side effects are manageable, not adversely affecting the patients' quality of life compared to ADT alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of apalutamide in the treatment landscape for patients with advanced prostate cancer: an expert opinion statement of European clinical practice. Bögemann, M., Facchini, G., Bauernhofer, T., et al.[2023]

References

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

Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials. [2023]

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

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer. [2023]

5. 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]

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

Apalutamide: First Global Approval. [2019]

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

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. [2023]

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

Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: a systematic review with pairwise and network meta-analyses. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

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

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2020]

11. Ireland pubmed.ncbi.nlm.nih.gov

Role of apalutamide in the treatment landscape for patients with advanced prostate cancer: an expert opinion statement of European clinical practice. [2023]