JNJ-78278343 + Cetrelimab for Prostate Cancer

Recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment that combines JNJ-78278343 (an experimental treatment) with cetrelimab (a type of immunotherapy) to help people with metastatic castration-resistant prostate cancer (mCRPC), which has spread and no longer responds to hormone therapy. In its early stages, the trial focuses on determining the best dose and assessing safety. Different groups may receive JNJ-78278343 with other agents like cabazitaxel or docetaxel. The trial seeks participants with a confirmed prostate cancer diagnosis, measurable disease, and prior treatment with specific cancer medications. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that JNJ-78278343, also known as pasritamig, is generally well-tolerated. In earlier studies, less than 10% of patients experienced a mild reaction called CRS (cytokine release syndrome), with all cases being grade 1, the least severe level. This indicates that most people can handle the treatment.

Specific safety data on its combination with cetrelimab is not available from past studies. However, since this trial is in an early stage, the main goal is to find the safest dose. Researchers are closely monitoring for any side effects to ensure participant safety. Overall, evidence so far indicates that patients are managing the treatments well, but ongoing research will provide clearer answers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for prostate cancer focus on hormonal therapy or chemotherapy. However, JNJ-78278343, combined with cetrelimab, is unique because it targets the disease differently. JNJ-78278343 is an innovative agent that researchers believe could work more effectively by focusing on a novel target in cancer cells, potentially enhancing the immune system's ability to attack the cancer. Cetrelimab is a checkpoint inhibitor that helps the immune system recognize and fight cancer cells more effectively. Researchers are excited about this combination because it could offer a powerful one-two punch against prostate cancer, potentially improving outcomes for patients who haven't responded well to standard therapies.

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

Research shows that combining JNJ-78278343, also known as pasritamig, with cetrelimab may effectively treat prostate cancer. In this trial, participants will receive JNJ-78278343 along with a combination agent, which may include cetrelimab. Pasritamig targets both cancer cells and T cells, aiding the immune system in fighting the cancer. Early studies have found that pasritamig is generally well-tolerated and has demonstrated strong anti-tumor effects in patients with advanced prostate cancer. This combination has also produced lasting results, helping to prevent the cancer from worsening over time. While more research is needed, these early findings offer hope for patients with prostate cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5017

Phase 1 study results of JNJ-78278343 (pasritamig) in ...

Pasritamig is a first-in-class T-cell-redirecting bispecific antibody that simultaneously binds KLK2 on PC cells and CD3 receptor complexes on T cells.

2.

jnj.com

jnj.com/media-center/press-releases/johnson-johnson-unveils-first-in-human-results-for-pasritamig-showing-early-anti-tumor-activity-in-prostate-cancer

Pasritamig, a first-in-class bispecific T-cell-engaging ...

Pasritamig appears well-tolerated and exhibits a promising antitumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC).

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05818683

NCT05818683 | A Study of JNJ-78278343 in Combination ...

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 ...

4.

urotoday.com

urotoday.com/conference-highlights/asco-2025/asco-2025-prostate-cancer/160809-asco-2025-phase-1-study-results-of-jnj-78278343-pasritamig-in-mcrpc.html

Phase 1 Study Results of JNJ-78278343 (Pasritamig) in ...

Pasritamig demonstrated a remarkable safety profile: · Pasritamig achieved durable responses and radiographic progression free survival that ...

5.

isrctn.com

isrctn.com/ISRCTN11926317

A study of JNJ-78278343 in combination with ...

Although treatments are available, they do not cure cancer. Over time, disease gets worse and progresses to metastatic castration-resistant prostate cancer ( ...