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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining golimumab and apalutamide in treating prostate cancer that no longer responds to traditional hormone therapies. Golimumab, an anti-inflammatory drug, reduces inflammation by blocking a specific substance in the body, while apalutamide stops cancer growth by blocking male hormones. The trial seeks participants with prostate cancer that progresses despite hormone treatments such as abiraterone or enzalutamide. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Previous studies have shown that apalutamide presents no new safety concerns and patients with prostate cancer tolerate it well. Real-world evidence also supports its safety, with many patients using it effectively without major issues.

Golimumab, used to treat inflammation, is generally well-tolerated. Its safety is well-established in treating other conditions. When combined, these two drugs have not led to unexpected problems, and most patients manage the side effects well. Always consult a healthcare provider about possible risks before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about combining golimumab and apalutamide for prostate cancer because this approach targets the condition in a unique way. Unlike traditional treatments that primarily focus on hormone therapy or chemotherapy, golimumab is an immune modulator that helps the immune system better recognize and attack cancer cells. Apalutamide, on the other hand, blocks the action of androgens, which fuel prostate cancer growth. By combining these two mechanisms, the treatment holds the potential to enhance effectiveness and possibly overcome resistance seen in standard therapies.

What evidence suggests that golimumab and apalutamide might be effective treatments for prostate cancer?

This trial will evaluate the combination of golimumab and apalutamide for prostate cancer. Studies have shown that apalutamide effectively treats prostate cancer by blocking androgens, hormones that help cancer cells grow. Apalutamide has improved progression-free survival, delaying the time before the cancer worsens. Specifically, one study found that apalutamide reduced the risk of death by 23% over two years for patients with certain types of prostate cancer. Golimumab blocks a substance called TNF, which causes inflammation and can aid cancer growth. Researchers believe that combining golimumab with apalutamide may effectively manage castration-resistant prostate cancer, potentially improving patient outcomes. ^{1 2 4 5 6}

Who Is on the Research Team?

Ruben Raychaudhuri, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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

Receiving other investigational agents within 14 days prior to enrollment

Infected joint prosthesis

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05960578

Golimumab and Apalutamide for the Treatment of ... Study Overview. Brief Summary. This phase II trial tests how well golimumab and apalutamide work in treating patients with castration resistant prostate cancer.

2. withpower.com withpower.com/trial/phase-2-adenocarcinoma-11-2023-9ffd2

Golimumab + Apalutamide for Prostate Cancer Apalutamide also enhanced second progression-free survival (PFS2) by 45%, indicating its efficacy in delaying disease progression, with no new safety concerns ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/apalutamide?pn=1

Clinical Trials Using Apalutamide - NCI NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying apalutamide.

4. jnj.com jnj.com/media-center/press-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11497945/

Real-world clinical outcomes among patients with ... This real-world study supported the real-world effectiveness of apalutamide based on data from 176 patients with metastatic castration-sensitive prostate cancer ...

6. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_14860.golimumab-and-apalutamide-for-the-treatment-of-castration-resistant-prostate-cancer-tramp-study.html

Clinical Trial Details This phase II trial tests how well golimumab and apalutamide work in treating patients with castration resistant prostate cancer.