JNJ-78278343 + Cetrelimab for Prostate Cancer

Recruiting at 13 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must be taking: Androgen receptor inhibitors

Must not be taking: Immunosuppressive medications

Disqualifiers: Autoimmune disease, Transplantation, Allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

185 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions prior treatment with certain medications, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug JNJ-78278343 + Cetrelimab for prostate cancer?

Research suggests that immune checkpoint inhibitors, like those in the treatment, may benefit certain prostate cancer patients, especially those with specific immune markers. However, the effectiveness can vary, and careful patient selection is important to identify those who might benefit. ^{1 2 3 4 5}

How is the drug JNJ-78278343 + Cetrelimab unique for prostate cancer treatment?

The drug JNJ-78278343 + Cetrelimab is unique because it combines a novel approach of targeting prostate cancer cells with a bispecific antibody that engages both PSMA on tumor cells and CD3 on T cells, potentially overcoming the immunosuppressive environment of prostate cancer and enhancing the body's immune response against the tumor. ^{6 7 8 9 10}

What is the purpose of this trial?

The purpose of this study is to identify the recommended phase 2 regimen(s) RP2R(s) of JNJ-78278343 and combination agent in Part 1 (dose escalation) and to determine safety at the putative RP2R(s) of JNJ-78278343 with the combination agent in Part 2 (dose expansion).

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for men with advanced prostate cancer that's resistant to hormone therapy and has spread. They should have tried at least one other treatment like abiraterone or chemotherapy, be relatively healthy (ECOG status of 0 or 1), and have adequate organ function. Men can't join if they've had recent autoimmune disease treatments, unresolved side effects from previous cancer therapies (except minor nerve damage or hair loss), transplants, serious infections, heart/lung problems, or allergies to the drugs being tested.

Inclusion Criteria

My cancer can be measured or seen on tests.

My prostate cancer has spread and does not respond to hormone therapy.

My organs are functioning well.

Exclusion Criteria

I do not have serious infections or major heart, lung, or other health issues.

My side effects from previous cancer treatments have mostly gone away.

Active autoimmune disease within the 12 months prior to signing consent that requires systemic immunosuppressive medications

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive JNJ-78278343 and combination agent with dose escalation to determine the recommended phase 2 regimen

Up to 21 days

Multiple visits (in-person)

Dose Expansion

Participants receive JNJ-78278343 and combination agent at the putative RP2R to assess safety and efficacy

Up to 2 years 11 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cetrelimab
• JNJ-78278343

Trial Overview The study is testing a combination of two drugs: JNJ-78278343 and Cetrelimab in patients with metastatic castration-resistant prostate cancer. The first part will find the best doses to use while checking safety. The second part will see how safe these doses are when more people take them.

Participant Groups

Group I: JNJ-78278343 + Combination agent: Part 1 (Dose Escalation) and Part 2 (Dose Expansion) Experimental Treatment 8 Interventions

Participants will receive JNJ-78278343 and combination agent (cetrelimab, cabazitaxel, docetaxel, apalutamide, enzalutamide, Darolutamide, abiraterone acetate plus prednisone) during Part 1 (dose escalation). The dose of JNJ-78278343 will be escalated sequentially until a recommended phase 2 regimen (RP2R). Participants will receive JNJ-78278343 and combination agent treatment at the putative RP2R in Part 2 (dose expansion).

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Immune checkpoint inhibitors have shown limited survival benefits in prostate cancer due to the tumor-immune microenvironment, which is characterized by low tumor-specific antigens and a high presence of tumor-associated macrophages.

To enhance the effectiveness of immunotherapies in prostate cancer, promising strategies include combining different immunotherapeutic agents, integrating immunotherapy with other treatment modalities, and developing biomarkers to identify patients who are most likely to benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding the tumor-immune microenvironment in prostate cancer. Dong, L., Myers, KV., Pienta, KJ.[2021]

In a study of 326 prostate adenocarcinoma patients from Spain and Norway, high expression of the immune checkpoint protein B7-H3 was linked to worse outcomes, including biochemical and clinical recurrence, indicating its potential as a target for immunotherapy.

Unlike B7-H3, PD-L1 expression did not show a correlation with clinical outcomes, suggesting that B7-H3 may be a more relevant biomarker for treatment strategies in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer. Nunes-Xavier, CE., Kildal, W., Kleppe, A., 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]

In a phase II study of 28 men with metastatic castration-resistant prostate cancer (mCRPC) who were progressing on enzalutamide, the combination of enzalutamide and the PD-1 inhibitor pembrolizumab resulted in a 50% or greater decline in prostate-specific antigen (PSA) levels in 18% of patients, indicating some efficacy of this combination therapy.

The study found that responses to the treatment were deep and durable, with a median overall survival of 21.9 months for all patients, and 41.7 months for those who responded, suggesting that pembrolizumab can be effective even without detectable PD-L1 expression or DNA-repair defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II single-arm study of pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer progressing on enzalutamide alone. Graff, JN., Beer, TM., Alumkal, JJ., et al.[2021]

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]

JNJ-63576253 is a newly discovered next-generation androgen receptor (AR) pathway inhibitor that effectively blocks AR signaling in prostate cancer models, addressing resistance mechanisms seen with current treatments.

This drug is being developed as a clinical candidate specifically for patients with metastatic castration-resistant prostate cancer (mCRPC) who do not respond to or are progressing on existing second-generation AR-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of JNJ-63576253, a Next-Generation Androgen Receptor Antagonist Active Against Wild-Type and Clinically Relevant Ligand Binding Domain Mutations in Metastatic Castration-Resistant Prostate Cancer. Branch, JR., Bush, TL., Pande, V., et al.[2021]

In a phase 1 study involving 39 patients with metastatic castration-resistant prostate cancer, the bispecific antibody JNJ-63898081 (JNJ-081) showed potential by causing transient decreases in PSA levels, indicating some antitumor activity.

Cytokine release syndrome (CRS) and infusion-related reactions (IRR) were observed but could be reduced with subcutaneous dosing and step-up priming, suggesting a safer administration method for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Study of Safety and Preliminary Clinical Activity of JNJ-63898081, a PSMA and CD3 Bispecific Antibody, for Metastatic Castration-Resistant Prostate Cancer. Lim, EA., Schweizer, MT., Chi, KN., et al.[2023]

JNJ-26146900 is a nonsteroidal androgen receptor antagonist that effectively reduces prostate weight and tumor growth in rat models, showing similar potency to the established drug bicalutamide.

In addition to its anti-cancer effects, JNJ-26146900 significantly prevents bone loss and maintains lean body mass in orchidectomized rats, suggesting potential anabolic benefits for bone and muscle health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats. Allan, G., Lai, MT., Sbriscia, T., et al.[2019]

Chronic treatment with the broad-spectrum AR antagonist JNJ-pan-AR can lead to resistance in prostate cancer cells, with specific enzymes like AKR1C3 identified as key drivers of this resistance.

Targeting AKR1C3 may enhance the effectiveness of antiandrogens and help prevent disease progression in castration-resistant prostate cancer (CRPC), suggesting a potential new therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AKR1C3 mediates pan-AR antagonist resistance in castration-resistant prostate cancer. Hertzog, JR., Zhang, Z., Bignan, G., et al.[2021]

Enzalutamide, an antiandrogen for castrate-resistant prostate cancer, leads to resistance through hyperactivation of Jak2-Stat5 signaling, creating a feedback loop that promotes cancer growth.

Targeting Jak2-Stat5 signaling with specific inhibitors can effectively induce cell death in enzalutamide-resistant prostate cancer, suggesting a promising new treatment strategy for patients who no longer respond to enzalutamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-Induced Feed-Forward Signaling Loop Promotes Therapy-Resistant Prostate Cancer Growth Providing an Exploitable Molecular Target for Jak2 Inhibitors. Udhane, V., Maranto, C., Hoang, DT., et al.[2021]

References

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

Understanding the tumor-immune microenvironment in prostate cancer. [2021]

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

Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer. [2022]

3. 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]

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

A phase II single-arm study of pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer progressing on enzalutamide alone. [2021]

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

Anti-PD-L1 plus enzalutamide does not improve overall survival in prostate cancer. [2023]

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

Discovery of JNJ-63576253, a Next-Generation Androgen Receptor Antagonist Active Against Wild-Type and Clinically Relevant Ligand Binding Domain Mutations in Metastatic Castration-Resistant Prostate Cancer. [2021]

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

Phase 1 Study of Safety and Preliminary Clinical Activity of JNJ-63898081, a PSMA and CD3 Bispecific Antibody, for Metastatic Castration-Resistant Prostate Cancer. [2023]

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

A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats. [2019]

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

AKR1C3 mediates pan-AR antagonist resistance in castration-resistant prostate cancer. [2021]

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

Enzalutamide-Induced Feed-Forward Signaling Loop Promotes Therapy-Resistant Prostate Cancer Growth Providing an Exploitable Molecular Target for Jak2 Inhibitors. [2021]