Key Messages
- •JNJ-63898081 (JNJ-081) is a bispecific antibody designed to form an immune synapse between PSMA-expressing tumor cells and CD3-expressing T cells.
- •In this phase 1 study, subcutaneous JNJ-081 was associated with prevalent anti-drug antibody formation.
- •Although dose escalation did not reach its full potential, this study contributed to our understanding of both the safety profile and tumor targeting with an anti-PSMA and CD3 bispecific in patients with metastatic resistant prostate cancer.
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.
Keywords
Abbreviations:
ARSI (androgen receptor synthesis inhibitor), CRS (cytokine release syndrome), ECOG PS (European Eastern Cooperative Oncology Group Performance Status), IRR (infusion-related reaction), MABEL (minimum anticipated biological effect level), mCRPC (metastatic castration-resistant prostate cancer), PSMA (prostate-specific membrane antigen), PSA (prostate-specific antigen), PCWG3 (Prostate Cancer Clinical Trials Working Group 3), RECIST (Response Evaluation Criteria in Solid Tumors)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 27, 2023
Accepted:
February 22,
2023
Received in revised form:
February 16,
2023
Received:
January 4,
2023
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
