PSMA-targeted CD28 bispecific enters phase 1 trial in mCRPC

The first patient has been dosed in a phase 1 trial evaluating JANX013, an investigational prostate-specific membrane antigen (PSMA)-targeted, tumor-activated CD28 co-stimulatory bispecific, in combination with the company’s investigational PSMA-targeted T-cell engager JANX007 in patients with metastatic castration-resistant prostate cancer (mCRPC).

The first-in-human study is designed primarily to assess safety and tolerability, with pharmacokinetic, pharmacodynamic, biomarker, and preliminary efficacy assessments also planned. The trial represents an early assessment of whether adding tumor-restricted CD28 co-stimulation to a PSMA-directed CD3 T-cell engager can produce a clinically useful therapeutic effect.

Over time, the investigators plan to evaluate JANX013 in combination with additional prostate cancer candidates.

"Co-stimulation plays a critical role in promoting sustained T-cell function and persistence," said Simon Butikofer, MD, vice president of Clinical Development, Janux Therapeutics, in a news release on the study.¹ "JANX013 is designed to selectively deliver tumor-restricted co-stimulation in combination with our CD3 T cell engagers, with the goal of extending the durability of anti-tumor immune responses."

Trial evaluates JANX013 with JANX007

The phase 1 study (NCT07813637) is an open-label, multicenter, first-in-human trial evaluating JANX013 in combination with JANX007 in adult patients with mCRPC. The study is expected to enroll approximately 110 participants and includes dose-escalation and expansion components.² The primary focus is safety and tolerability, whereas secondary and exploratory assessments include pharmacokinetics, pharmacodynamics, antitumor activity, and immune biomarkers such as T-cell expansion and persistence.

The study population includes patients with mCRPC who have previously received at least 1 androgen receptor pathway inhibitor and, for dose escalation, either have received a taxane or are medically unsuitable for or have declined taxane therapy. The expansion population is intended to include patients in earlier lines of mCRPC treatment. The trial excludes patients with prior treatment with an approved or investigational T-cell engager or T-cell costimulatory agent, among other criteria.

JANX007 provides the combination backbone

JANX013 is being developed initially with JANX007, Janux's PSMA-targeted tumor activated T-cell engager (TRACTr). JANX007 is being studied in a phase 1 trial in patients with mCRPC.

"The initiation of the JANX013 clinical program represents an important milestone in the continued evolution of our prostate cancer franchise," said David Campbell, PhD, President and CEO of Janux Therapeutics, in the news release.¹ "By combining complementary tumor-activated immunotherapies, we believe we have an opportunity to further improve long-term outcomes for patients with prostate cancer."

REFERENCES

1. Janux Therapeutics announces first patient dosed in phase 1 study of JANX013. News release. Janux Therapeutics, Inc. September 14, 2026. Accessed September 14, 2026. https://www.businesswire.com/news/home/20260914249735/en/Janux-Therapeutics-Announces-First-Patient-Dosed-in-Phase-1-Study-of-JANX013

2. Phase 1 trial to study JANX013 and JANX007 combination in mCRPC (PSMA-013-001). ClinicalTrials.gov. Last updated September 10, 2026. Accessed September 14, 2026. https://clinicaltrials.gov/study/NCT07813637