ARX517 + Enzalutamide for Prostate Cancer

(ARX517 Trial)

Recruiting at 16 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must be taking: LHRH agonists

Must not be taking: Chemotherapy, Apalutamide

Disqualifiers: CNS metastases, Invasive malignancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1.5 years

183 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a new treatment called ARX517, either alone or combined with other drugs, for men with metastatic prostate cancer. Different groups will receive ARX517 alone, with apalutamide, or with abiraterone acetate and prednisone. Men whose prostate cancer has spread and worsened after previous treatments might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Do I need to stop my current medications for the trial?

The trial requires stopping certain medications before enrollment, such as chemotherapy within 21 days and hormonal therapy (except LHRH analogs) within 7 days. However, you must continue LHRH therapy if you are already on it.

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

Research shows that ARX517 appears safe for patients with advanced prostate cancer. Studies have found that ARX517 reduces prostate-specific antigen (PSA) levels without causing serious side effects, suggesting it is well-tolerated so far.

The safety of ARX517 combined with apalutamide, another prostate cancer treatment, is still under study. However, apalutamide alone has a good safety record. Research indicates that patients taking apalutamide have not experienced cancer recurrence for over two years in some cases, demonstrating its general safety.

For the combination of ARX517 with abiraterone acetate plus prednisone (AAP), abiraterone acetate is already used for prostate cancer and is known to be safe. Studies have shown that it helps patients live longer, supporting its safety.

As this study is in the early stages, it primarily focuses on safety, and early results suggest these treatments are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ARX517 for prostate cancer because it represents a novel approach compared to existing treatments. Unlike standard therapies that typically target hormone pathways, ARX517 is an antibody-drug conjugate, which means it can specifically deliver a powerful drug directly to cancer cells, potentially increasing effectiveness and reducing side effects. It's administered through intravenous infusion every three weeks, potentially offering an alternative to more frequent dosing schedules. Additionally, combining ARX517 with other agents like enzalutamide, apalutamide, or abiraterone acetate plus prednisone (AAP) may enhance its cancer-fighting abilities by attacking the disease from multiple angles.

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

Research has shown that ARX517, one of the treatments in this trial, may help treat advanced prostate cancer. Some patients have experienced significant drops in their prostate-specific antigen (PSA) levels, with reductions up to 91% after just one dose, suggesting that ARX517 could slow the disease.

In this trial, researchers are also studying ARX517 in combination with apalutamide, another treatment option. Together, ARX517 and apalutamide have led to substantial PSA reductions, with some patients experiencing drops of 90% or more. Apalutamide is already recognized as a safe and effective treatment for prostate cancer.

Another combination being tested in this trial is ARX517 with abiraterone acetate plus prednisone (AAP). AAP has been shown to help manage advanced prostate cancer, allowing patients to live longer without disease progression. These findings suggest that both combination treatments could effectively manage advanced 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 adult men with metastatic castration-resistant prostate cancer who have had at least two FDA-approved treatments, including one targeting androgen receptors. They must be on hormone therapy with low testosterone levels and have adequate blood counts. Men with brain metastases needing steroids, significant heart rhythm issues, serious eye conditions, other recent cancers, or lung diseases can't join.

Inclusion Criteria

I am on hormone therapy for cancer and my testosterone is low.

My prostate cancer was confirmed through a tissue examination.

My cancer has spread to other parts of my body.

Exclusion Criteria

My heart's electrical cycle is longer than normal.

I have serious eye problems confirmed by an eye doctor.

I haven't had lung diseases like interstitial lung disease or pneumonitis in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ARX517 as monotherapy or in combination with androgen receptor pathway inhibitors, administered via intravenous infusion every 3 weeks

1.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and pharmacokinetic parameters

3 years

What Are the Treatments Tested in This Trial?

Interventions

• ARX517

Trial Overview The study is testing ARX517 alone or combined with other drugs in men with advanced prostate cancer that resists standard hormonal treatment. It's an early-stage trial to see if these treatments are safe and how well patients tolerate them.

How Is the Trial Designed?

Group I: ARX517+Apalutamide Experimental Treatment 2 Interventions

ARX517 and apalutamide

Group II: ARX517+AAP Experimental Treatment 3 Interventions

ARX517 and abiraterone acetate plus prednisone(AAP)

Group III: ARX517 Experimental Treatment 1 Intervention

ARX517 will be administered via intravenous (IV) infusion, with the initial treatment regimen by weight-based infusion at an interval of every 3 weeks. Other treatment regimen may be explored.

ARX517 is already approved in United States for the following indications:

Approved in United States as ARX517 for:

• Metastatic castration-resistant prostate cancer (mCRPC) under Fast Track Designation, not yet fully approved

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

Ambrx, Inc.

Lead Sponsor

Trials

8

Recruited

860+

Johnson & Johnson

Industry Sponsor

Trials

116

Recruited

167,000+

Published Research Related to This Trial

Enzalutamide significantly improves overall survival and radiographic progression-free survival in men with metastatic, castration-resistant prostate cancer (mCRPC), as shown in two major randomized trials (AFFIRM and PREVAIL) involving patients who had previously undergone chemotherapy and those who were chemotherapy naive.

While enzalutamide is generally safe and effective, it can cause side effects like fatigue and has specific safety concerns, such as an increased risk of seizures and falls, particularly in older patients (≥ 75 years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. Graff, JN., Gordon, MJ., Beer, TM.[2021]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

In a study of 48 men with intermediate or high-risk localized prostate cancer, the combination therapy of enzalutamide, dutasteride, and leuprolide resulted in a pathologic complete response (pCR) rate of 4.3% and minimal residual disease (MRD) in 13.0% of patients, indicating some effectiveness in reducing cancer prior to surgery.

In contrast, the enzalutamide-only group showed no patients achieving pCR or MRD, and had a higher median residual cancer burden, suggesting that the combination therapy may be more effective in managing prostate cancer by better targeting androgen receptor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Enzalutamide Prior to Prostatectomy. Montgomery, B., Tretiakova, MS., Joshua, AM., et al.[2021]

Enzalutamide-resistant prostate cancer (ENZ-R CRPC) cells show high levels of both full-length androgen receptor (ARFL) and its variant AR-V7, with ARFL being the primary driver of resistance, as evidenced by a 12-fold higher expression in ENZ-R-LNCaP cells compared to CRPC-LNCaP cells.

Targeting both ARFL and AR variants using antisense oligonucleotides effectively induced apoptosis, suppressed cell growth, and delayed tumor growth in various CRPC models, suggesting that combined AR targeting strategies could be a promising approach for treating AR-dependent CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation 2.5 antisense oligonucleotides targeting the androgen receptor and its splice variants suppress enzalutamide-resistant prostate cancer cell growth. Yamamoto, Y., Loriot, Y., Beraldi, E., et al.[2022]

In a study of 14 Japanese patients with castration-resistant prostate cancer (CRPC), enzalutamide (ENZ) demonstrated a high efficacy, with 92% of patients achieving a significant reduction in prostate-specific antigen (PSA) levels of 50% or more from baseline.

The safety profile of ENZ was favorable, with only mild adverse events occurring in more than 20% of patients, indicating that even reduced doses of ENZ (80 or 120 mg/day) are effective and safe for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Enzalutamide in a Real-World Cohort of Japanese Patients With Castration-resistant Prostate Cancer. Hori, A., Sahashi, H., Sano, S., et al.[2021]

The PREVAIL Phase 3 trial demonstrated that enzalutamide significantly improves radiographic-progression free survival in men with castration-resistant prostate cancer (CRPC), with 65% of patients showing no progression compared to those on placebo.

Enzalutamide also provided a median overall survival benefit of 32.4 months versus 30.2 months for the placebo group, indicating its efficacy as a treatment option before chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for treatment of CRPC: rationale for sequencing and potential clinical biomarker for resistance. Lochrin, SE., Figg, WD., Finn, SP.[2020]

Enzalutamide (Enz) therapy can extend the lives of patients with castration-resistant prostate cancer (CRPC) by an average of 4.8 months, but many patients eventually develop resistance to this treatment.

The AR degradation enhancer ASC-J9(®) shows promise as a new therapy by effectively targeting and degrading the androgen receptor mutant AR-F876L, which is linked to Enz resistance, potentially improving outcomes for patients with CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASC-J9(®) suppresses castration resistant prostate cancer progression via degrading the enzalutamide-induced androgen receptor mutant AR-F876L. Wang, R., Lin, W., Lin, C., et al.[2021]

JJ-450 is a novel androgen receptor antagonist that effectively inhibits both wild-type and enzalutamide-resistant ARF876L mutant activity in prostate cancer cells, unlike enzalutamide which fails to inhibit the mutant.

In laboratory tests, JJ-450 not only blocked the proliferation of prostate cancer cells expressing the ARF876L mutation but also prevented its nuclear translocation, suggesting it could be a promising treatment for castration-resistant prostate cancer that has become resistant to enzalutamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel androgen receptor antagonist JJ-450 inhibits enzalutamide-resistant mutant ARF876L nuclear import and function. Wu, Z., Wang, K., Yang, Z., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04662580

Study Details | NCT04662580 | ARX517/JNJ-95298177 as ... This is a phase 1 study to assess the safety and tolerability of ARX517 as monotherapy or combination therapy in adult subjects with metastatic prostate cancer ...

2. onclive.com onclive.com/view/arx517-demonstrates-early-efficacy-with-favorable-safety-in-heavily-pretreated-mcrpc

ARX517 Demonstrates Early Efficacy With Favorable ... Patients who received the ADC experienced deep PSA reductions with increasing doses of the agent; 61%, 52%, and 26% of those in cohorts 6 to 8 ( ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03589-5/fulltext

1804P APEX-01: First-in-human phase I/II study of ARX517 ... Conclusions. ARX517 treatment resulted in PSA declines and RECIST v1. 1 responses without treatment-related SAEs. Dose expansion has begun, additional safety, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11612621/

Preclinical Characterization of ARX517, a Site-Specific ... ARX517 exhibited a long terminal half-life and high serum exposure in mice and dose-dependent antitumor activity in both enzalutamide-sensitive and -resistant ...

5. targetedonc.com targetedonc.com/view/arx517-shows-promising-safety-and-efficacy-in-mcrpc

ARX517 Shows Promising Safety and Efficacy in mCRPC Two of 3 patients receiving 3.4 mg/kg of ARX517 had prostate specific antigen (PSA) reductions of 91% and 33% at 3 weeks after receiving 1 dose.