PSMA-targeted T-cell engager enters phase 1 testing in mCRPC

A novel prostate-specific membrane antigen (PSMA)-targeted T-cell engager has entered early clinical development for metastatic castration-resistant prostate cancer (mCRPC). According to Janux Therapeutics, the first patient has been dosed in a phase 1 trial evaluating JANX014, an investigational double-masked T-cell engager designed to activate T cells preferentially within the tumor microenvironment.¹

JANX014 is designed with both the PSMA-binding and CD3 domains masked, an approach intended to enable tumor-selective T-cell activation and potentially improve safety over traditional T-cell engager approaches in prostate cancer, including reducing the risk of cytokine release syndrome (CRS).²

According to the company, the study is a first-in-human, open-label, multicenter phase 1 trial assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of JANX014 in adult patients with mCRPC. Participants in the trial will receive ascending doses of JANX014 as a single agent.³

Additional trial platforms

JANX014 is intended to serve as an extension of the work being done with JANX007, the company’s lead PSMA-directed T-cell engager already in phase 1 testing.

Janux Therapeutics previously reported interim data from the phase 1 trial of JANX007, showing a manageable safety profile with no grade 3 CRS at clinically relevant doses. The agent also demonstrated preliminary antitumor activity, with 83% of patients achieving a prostate-specific antigen decline of at least 50% (PSA50) with a first step dose of 0.2 mg or higher and 56% achieving a PSA50 decline with a first step dose of 0.1 mg or higher.⁴

Related: Immunotherapies show safety and efficacy in mCRPC, renal cell carcinoma

The move into JANX014 is an effort to evaluate multiple PSMA-directed approaches across prostate cancer. According to the company, JANX014 “will also explore potential future use cases where enhanced safety margins and ease of administration may be particularly important.”

“We are pleased to have initiated clinical evaluation of JANX014,” David Campbell, PhD, president and CEO of Janux Therapeutics, said in the news release.¹ “JANX007 remains our lead prostate program, and we believe it has established a strong clinical foundation for PSMA-directed TRACTr [tumor-activated T-cell engager] therapy. Insights from programs such as JANX007 and JANX008 have informed our continued platform development. We are building a prostate cancer portfolio designed to address patients across multiple stages of disease, including both single and combination approaches. Advancing programs such as JANX014 reflects our strategy of expanding on that foundation while maintaining disciplined execution on our lead program.”

The company also plans to open an additional trial exploring JANX013, a PSMA-TRACIr CD28 costimulatory program in mCRPC, in the second half of 2026.

“Janux’s tumor-activated technology allows us to evaluate multiple molecular designs against the same validated target,” William Go, MD, PhD, chief medical officer of Janux Therapeutics, said in the release.¹ “As we advance JANX007, we are also developing complementary approaches within our platforms, including JANX013, our CD28 costimulatory PSMA-TRACIr program, along with exploratory approaches like JANX014. This innovative work is intended to help us understand how different mechanisms and masking strategies may translate into clinical benefit across patient populations in prostate cancer.”

REFERENCES

1. Janux Therapeutics announces first participant dosed in phase 1 study of JANX014. News release. Janux Therapeutics. April 16, 2026. Accessed April 20, 2026. https://investors.januxrx.com/investor-media/news/news-details/2026/Janux-Therapeutics-Announces-First-Participant-Dosed-in-Phase-1-Study-of-JANX014/default.aspx
2. PSMA-TRACTr (JANX014). Janux Therapeutics. Accessed April 20, 2026. https://www.januxrx.com/psma-tractr-janx014/
3. Clinical trials. Janux Therapeutics. Accessed April 20, 2026. https://www.januxrx.com/clinical-trials/
4. Janux announces encouraging safety and efficacy data in ongoing dose escalation trials for PSMAxCD3-TRACTr JANX007 in mCRPC and EGFRxCD3-TRACTr JANX008 in solid tumors. News release. Janux Therapeutics. February 26, 2024. Accessed April 20, 2026. https://investors.januxrx.com/investor-media/news/news-details/2024/Janux-Announces-Encouraging-Safety-and-Efficacy-Data-in-Ongoing-Dose-Escalation-Trials-for-PSMAxCD3-TRACTr-JANX007-in-mCRPC-and-EGFRxCD3-TRACTr-JANX008-in-Solid-Tumors/default.aspx