JNJ Combo for Prostate Cancer

Recruiting at 7 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must be taking: GnRH analogs

Must not be taking: Immunosuppressants

Disqualifiers: Autoimmune disease, Heart conditions, others

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

Compensation: Varies

Number of Visits: Unknown

130 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to determine the recommended regimen for Phase 2 (RP2Rs) of combination of JNJ-87189401 with JNJ-78278343 (Part 1: dose escalation) and further evaluate the safety at RP2Rs (Part 2: dose expansion) in participants with advanced prostate cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must continue androgen deprivation therapy if you are already on it. If you have an active autoimmune disease requiring certain medications, you may not be eligible to participate.

What data supports the effectiveness of the drug JNJ-78278343 and JNJ-87189401 for prostate cancer?

The research does not provide direct evidence for the effectiveness of JNJ-78278343 and JNJ-87189401 in prostate cancer, but it mentions that docetaxel, a similar chemotherapy drug, has shown a survival benefit in metastatic prostate cancer, suggesting potential for combination therapies. ^{1 2 3 4 5}

What safety information is available for JAK inhibitors used in prostate cancer treatment?

JAK inhibitors, which are being explored for prostate cancer treatment, have shown an increased risk of infections like varicella-zoster (shingles) and potential adverse effects such as deep vein thrombosis (blood clots in veins) and pulmonary embolism (blood clots in lungs), especially in older patients with other health conditions. Both the US FDA and the European Medicines Agency have issued warnings about these risks, particularly for individuals over 50 with cardiovascular risk factors. ^{6 7 8 9 10}

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 who are still able to carry out daily activities (ECOG status of 0 or 1). They must have a specific type of cancer that has spread and is resistant to hormone therapy, with a PSA level over 2 ng/mL. Participants should either have had surgery to remove their testicles or be on hormone-blocking medication.

Inclusion Criteria

I am fully active or can carry out light work.

My PSA level is 2 ng/mL or higher and my disease can be measured.

I have undergone orchiectomy or am on hormone therapy for prostate cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive JNJ-78278343+JNJ-87189401 with dose escalation to determine the recommended Phase 2 regimen (RP2R)

Up to 21 days

Dose Expansion

Participants receive the combination treatment at the RP2R to further evaluate safety

Up to 3 years 7 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• JNJ-78278343
• JNJ-87189401

Trial Overview The study tests combining two drugs, JNJ-87189401 and JNJ-78278343, in men with advanced prostate cancer. The first part determines the best doses for safety and effectiveness, while the second part further examines safety at these doses.

Participant Groups

Group I: Part 1 (Dose Escalation) and Part 2 (Dose Expansion) Experimental Treatment 2 Interventions

Participants will receive JNJ-78278343+JNJ-87189401 escalated sequentially in Part 1 to select a recommended Phase 2 regimen (RP2R). Participants will receive the combination treatment at the 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

In a review of five randomized-controlled trials involving 5427 patients with metastatic castration-sensitive prostate cancer (mCSPC), androgen-receptor-axis-targeted (ARAT) agents significantly improved overall survival (OS) with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death compared to standard androgen deprivation therapy (ADT).

The study suggests that combining ARAT agents with docetaxel may not be beneficial, as differential outcomes were observed based on tumor volume and the presence of visceral metastasis, indicating that treatment strategies should be tailored based on these factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of efficacy of androgen-receptor-axis-targeted therapies in patients with metastatic castration-sensitive prostate cancer: A systematic review and meta-analysis. Buonerba, C., Ferro, M., Dolce, P., et al.[2020]

Upadacitinib (UPA) demonstrated significant efficacy in treating psoriatic arthritis (PsA), with placebo-subtracted improvements in ACR criteria of 33.7% to 45.7% after 12 weeks, regardless of whether it was used alone or with non-biologic DMARDs.

The safety profile of UPA was generally consistent between monotherapy and combination therapy, although there was a higher incidence of hepatic disorders and creatine phosphokinase elevation in patients receiving combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Nash, P., Richette, P., Gossec, L., et al.[2022]

Docetaxel (DOC) therapy significantly improves overall survival (OS) in Japanese patients with castration-resistant prostate cancer (CRPC), with a median OS of 94 months compared to 70 months for those receiving conventional androgen-deprivation therapy (ADT).

Higher doses of DOC (≥70 mg/m²) also lead to longer OS compared to lower doses and control, with no reported deaths due to DOC therapy, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can docetaxel therapy improve overall survival from primary therapy compared with androgen-deprivation therapy alone in Japanese patients with castration-resistant prostate cancer? A multi-institutional cooperative study. Shimabukuro, T., Sakano, S., Matsuda, K., et al.[2022]

In a phase III trial involving 950 patients with metastatic castrate-refractory prostate cancer, oral satraplatin significantly reduced the risk of disease progression or death by 33% compared to placebo, indicating its efficacy in delaying disease progression.

While satraplatin did not improve overall survival compared to placebo, it effectively delayed pain progression and was generally well tolerated, although some patients experienced more frequent side effects like myelosuppression and gastrointestinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. Sternberg, CN., Petrylak, DP., Sartor, O., et al.[2022]

Docetaxel-based therapy has been shown to provide a survival benefit for men with metastatic prostate cancer, marking a significant advancement beyond palliative care options.

Ongoing trials are exploring various combination therapies with docetaxel, but the best timing for initiating treatment remains unclear due to a lack of prospective clinical trial data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. Petrylak, DP.[2022]

Docetaxel is the first-line treatment for metastatic castration-resistant prostate cancer, but its effectiveness is often limited by dose-limiting toxicities such as neutropenia and neurotoxicity.

Research identified Janus kinase 1 (JAK1) as a promising target to enhance docetaxel sensitivity, showing that JAK1 inhibitors can synergize with docetaxel to increase cancer cell apoptosis, particularly in androgen receptor-negative prostate cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells. Nalairndran, G., Chung, I., Abdul Razack, AH., et al.[2022]

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]

Tofacitinib, a JAK1-3 inhibitor approved by the FDA, has been shown to inhibit the histone kinase PRK1 in both laboratory and cellular settings, suggesting its potential as a treatment for prostate cancer.

Through structure-activity relationship studies, researchers identified a more potent and selective PRK1 inhibitor than tofacitinib, along with two selectivity hotspots that could guide the development of future PRK1-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib and analogs as inhibitors of the histone kinase PRK1 (PKN1). Ostrovskyi, D., Rumpf, T., Eib, J., et al.[2018]

Androgen deprivation therapy (ADT) for metastatic prostate cancer can lead to the development of castrate-resistant prostate cancer (CRPC), which often reactivates the androgen receptor (AR), necessitating the use of second-generation anti-androgens like enzalutamide (ENZ).

Inhibition of the Jak2-Stat5 signaling pathway has been shown to induce apoptosis in prostate cancer cells and may provide a new therapeutic target, especially since Jak2-Stat5 activity is linked to resistance against ENZ and predicts cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development? Beinhoff, P., Sabharwal, L., Udhane, V., et al.[2022]

JAK inhibitors are effective for treating autoimmune diseases like rheumatoid arthritis, but they carry an increased risk of infections, particularly reactivation of varicella-zoster virus.

Older patients, especially those over 50 with cardiovascular risk factors, face heightened risks of serious adverse effects such as deep vein thrombosis and pulmonary embolism, leading to black box warnings from the FDA regarding these potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Janus Kinase Inhibitors in Older Patients: A Focus on the Thromboembolic Risk. Rajasimhan, S., Pamuk, O., Katz, JD.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Predictors of efficacy of androgen-receptor-axis-targeted therapies in patients with metastatic castration-sensitive prostate cancer: A systematic review and meta-analysis. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Can docetaxel therapy improve overall survival from primary therapy compared with androgen-deprivation therapy alone in Japanese patients with castration-resistant prostate cancer? A multi-institutional cooperative study. [2022]

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

Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. [2022]

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

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells. [2022]

7. 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]

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

Tofacitinib and analogs as inhibitors of the histone kinase PRK1 (PKN1). [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development? [2022]

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

Safety of Janus Kinase Inhibitors in Older Patients: A Focus on the Thromboembolic Risk. [2021]