Johnson & Johnson Completes Phase 1 Clinical Trial of JNJ-75229414, a CAR-T Therapy Targeting Metastatic Castration-Resistant Prostate Cancer
The Rise of a Novel Target: KLK2
JNJ-75229414, developed by Johnson & Johnson's (JNJ) subsidiary Janssen, is the first chimeric antigen receptor T-cell (CAR-T) therapy targeting Kallikrein-2 (KLK2), a prostate-specific antigen. In the treatment market for metastatic Castration-Resistant Prostate Cancer (mCRPC), it establishes a unique target compared to most pipelines that target Prostate-Specific Membrane Antigen (PSMA). KLK2 is a protein overexpressed in androgen receptor (AR)-signaling-active cancer cells and is also expressed in normal tissues such as the salivary gland, making it a promising alternative target to PSMA, which can cause side effects. This trial can be understood as an attempt to provide a new treatment pathway for patients with progressive prostate cancer who have failed standard treatment.
Successful Completion and Significance of the Phase 1 Trial
The completed Phase 1 clinical trial (NCT05022849) was conducted to evaluate the safety and tolerability of JNJ-75229414 and to determine the Recommended Phase 2 Dose (RP2D). It began on September 28, 2021, and was officially completed on March 11, 2026, and included dose escalation and dose expansion phases. Due to the nature of autologous CAR-T therapy, which involves genetically modifying a patient's own T cells to attack cancer cells, ease of manufacturing and control of toxicities such as Cytokine Release Syndrome (CRS) are key to commercialization. Through this trial, Janssen has demonstrated the safety of the target antigen, laying the foundation for establishing a presence in the prostate cancer field with cell therapies.
High-Growth Prostate Cancer Market and Unmet Needs
The mCRPC treatment market is estimated at approximately USD 21.04 billion in 2025 and is showing rapid growth of 8% to 15% per year due to aging and advances in diagnostic technology. Current standard of care (SoC) treatments include hormone therapies such as Xtandi and Zytiga, docetaxel chemotherapy, and Novartis' PSMA-targeted radioligand therapy, Pluvicto. However, as treatment continues, drug resistance develops, leading to a rapid deterioration in prognosis, and there is still a high unmet medical need. JNJ-75229414 was developed with the strategic goal of providing a near-curative treatment effect for patients with late-stage disease who are resistant to existing hormone and chemotherapy treatments.
Janssen's Diversified Prostate Cancer Portfolio
Johnson & Johnson is pursuing a two-pronged strategy, developing not only JNJ-75229414, an autologous CAR-T therapy targeting KLK2, but also Pasritamig (JNJ-78278343), a bispecific T-cell engager (TCE). Pasritamig is currently in Phase 3 clinical trials and is showing faster commercialization, while the CAR-T pipeline, JNJ-75229414, is in the early stages of development and is exploring potential synergies. This demonstrates the direction of platform enhancement by a major pharmaceutical company, which aims to overcome the challenges of the tumor microenvironment (TME) that CAR-T therapies face in the field of solid tumors by complementing them with bispecific antibody technology. The industry and academia are paying attention to how these two pipelines will change the landscape of the prostate cancer immuno-oncology market in the future.
The completion of this Phase 1 clinical trial is significant because it demonstrates the clinical safety of KLK2, a new target in the approximately USD 21.04 billion market for metastatic castration-resistant prostate cancer, and has long-term investment value. In a market where Novartis' Pluvicto and other PSMA-targeted therapies are leading the way, this provides an opportunity to secure a niche market and acquire patients who are resistant to drugs by differentiating the target. From a researcher's perspective, it has academic significance in that it provides initial data to overcome the immune-suppressive environment that autologous CAR-T therapies have in the field of solid tumors. In the short term, it will be an indicator to gauge the success of Johnson & Johnson's next-generation urological cancer treatment portfolio by cross-validating it with the results of the Phase 3 trial of the same target bispecific antibody pipeline, Pasritamig.
Source: ClinicalTrials.gov (api_ct)