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Cited by 62Prostate Cancer Treatment and ResearchCancer Immunotherapy and BiomarkersMonoclonal and Polyclonal Antibodies Research

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

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Lim, Emerson A., Schweizer, Michael T., Chi, Kim N., Aggarwal, Rahul, Agarwal, Neeraj, Gulley, James, Attiyeh, Edward, Greger, James +6 more·2023·Clinical Genitourinary Cancer
DOI 10.1016/j.clgc.2023.02.010PMC PMC10219845
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Abstract

Introduction Cancer immunotherapies have limited efficacy in prostate cancer due to the immunosuppressive prostate microenvironment. Prostate specific membrane antigen (PSMA) expression is prevalent in prostate cancer, preserved during malignant transformation, and increases in response to anti-androgen therapies, making it a commonly targeted tumor associated antigen for prostate cancer. JNJ-63898081 (JNJ-081) is a bispecific antibody targeting PSMA-expressing tumor cells and CD3-expressing T cells, aiming to overcome immunosuppression and promoting antitumor activity. Patients and methods We conducted a phase 1 dose escalation study of JNJ-081 in patients with metastatic castration-resistance prostate cancer (mCRPC). Eligible patients included those receiving ≥1 prior line treatment with either novel androgen receptor targeted therapy or taxane for mCRPC. Safety, pharmacokinetics, and pharmacodynamics of JNJ-081, and preliminary antitumor response to treatment were evaluated. JNJ-081 was administered initially by intravenous (IV) then by subcutaneous (SC) route. Results Thirty-nine patients in 10 dosing cohorts received JNJ-081 ranging from 0.3 µg/kg to 3.0 µg/kg IV and 3.0 µg/kg to 60 µg/kg SC (with step-up priming used at higher SC doses). All 39 patients experienced ≥1 treatment-emergent AE, and no treatment-related deaths were reported. Dose-limiting toxicities were observed in 4 patients. Cytokine release syndrome (CRS) was observed at higher doses with JNJ-081 IV or SC; however, CRS and infusion-related reaction (IRR) were reduced with SC dosing and step-up priming at higher doses. Treatment doses >30 µg/kg SC led to transient PSA decreases. No radiographic responses were observed. Anti-drug antibody responses were observed in 19 patients receiving JNJ-081 IV or SC. Conclusion JNJ-081 dosing led to transient declines in PSA in patients with mCRPC. CRS and IRR could be partially mitigated by SC dosing, step-up priming, and a combination of both strategies. T cell redirection for prostate cancer is feasible and PSMA is a potential therapeutic target for T cell redirection in prostate cancer.

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  • In a 2023 phase 1 study of 39 patients, JNJ-081 produced a PSA50 response of 7.7%.

    “JNJ- 081, an alternate BiTE targeting PSMA, was studied in a 2023 phase 1 study of 39 patients and showed a PSA50 response of 7.7%.”

    From PSMA-based Therapies and Novel Therapies in Advanced Prostate Cancer: The Now and the Future (2025) · cites this paper as [29]

    The Abstract (Results) confirms that 39 patients received JNJ-081 in this phase 1 study. The Results (Efficacy; page unavailable) report confirmed PSA declines greater than 50% in two patients, not a 7.7% PSA50 response rate; two of 39 is approximately 5.1%. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Every patient in the JNJ-081 phase 1 study experienced at least one TE-AE, and 19 patients developed TE-ADAs, ultimately resulting in early discontinuation of the trial.

    “Every patient in the study experienced at least one TE-AE, with 19 patients developing TE-ADAs ultimately resulting in early discontinuation of the trial”

    From PSMA-based Therapies and Novel Therapies in Advanced Prostate Cancer: The Now and the Future (2025) · cites this paper as [29]

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Authors
Lim, E. A., Schweizer, M. T., Chi, K. N., Aggarwal, R., Agarwal, N., Gulley, J., Attiyeh, E., Greger, J., Wu, S., Jaiprasart, P., Loffredo, J., Bandyopadhyay, N., Xie, H., & Hansen, A. R.
Affiliations
  • Columbia University Irving Medical Center (US)
  • University of Washington (US)
  • BC Cancer Agency (CA)
  • UCSF Helen Diller Family Comprehensive Cancer Center (US)
  • Huntsman Cancer Institute (US)
  • National Institutes of Health (US)
  • Janssen Research & Development (United States) (US)
  • Queensland Health (AU)
Corresponding author
Hansen, Aaron R.
ORCID
Venue
Clinical Genitourinary Cancer
Publisher
Elsevier BV
Published
2023-06
Volume
21
Issue
3
Pages
366-375
ISSN
1558-7673 (ISSN-L)
DOI
10.1016/j.clgc.2023.02.010
PMC
PMC10219845
OpenAlex
W4328095977
Cited by
62
References
3
Citations by year
2026: 16 · 2025: 22 · 2024: 13 · 2023: 10 · 2022: 1
FWCI
11.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Genitourinary Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (Z99 CA999999)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Keywords
prostate-specific membrane antigen, CD3 bispecific antibody, metastatic castration-resistant prostate cancer, T cell redirection, cytokine release syndrome, infusion reactions, subcutaneous dosing, anti-drug antibodies, immunosuppressive tumor microenvironment, dose-limiting toxicity, pharmacokinetics
MeSH terms
Antineoplastic Agents, Humans, Male, Treatment Outcome, Prostate-Specific Antigen, Tumor Microenvironment, Prostatic Neoplasms, Castration-Resistant

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