Phase 1 JANX013 PSMA×CD28 costimulation combines with JANX007 PSMA×CD3 T-cell engagement

Janux Therapeutics’ first-in-human Phase 1, open-label, multicenter study evaluates JANX013 plus JANX007 in adults with metastatic castration-resistant prostate cancer (mCRPC). JANX007 is a PSMA-directed, tumor-activated T-cell engager that brings CD3-positive T cells to prostate cancer cells. JANX013 is a tumor-activated PSMA-directed CD28 costimulatory molecule intended to supply an additional activation signal locally, rather than stimulating CD28 indiscriminately throughout the body.

Dose escalation and expansion assess safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity. The study includes androgen receptor pathway inhibitor (ARPI)-pretreated mCRPC cohorts, including earlier-line mCRPC. The central question is whether localized CD28 costimulation can strengthen or sustain PSMA-directed T-cell killing without unacceptable immune toxicity. Existing treatment choices after ARPI exposure include taxanes, molecularly selected PARP inhibitors, PSMA-targeted radioligand therapy for eligible patients, and other therapies selected according to previous treatment and disease features; this combination remains investigational.