Phase 2 JNJ-101556143 uses an AR-BRD4 induced-proximity mechanism in resistant prostate cancer

This Phase 2, open-label, multicenter, single-arm study tests once-daily oral JNJ-101556143, previously called HLD-0915, in metastatic androgen pathway modulation-resistant prostate cancer. The primary activity assessment is overall response evaluated by blinded independent central review. Janssen Research & Development, a Johnson & Johnson company, sponsors the program, which originated at Halda Therapeutics.

JNJ-101556143 is a Regulated Induced Proximity Targeting Chimera (RIPTAC): a heterobifunctional molecule that brings androgen receptor (AR) and BRD4 together in a ternary complex, impairing an essential BRD4-dependent function in AR-expressing cancer cells. Unlike protein degradation, this approach depends on disrupting protein function within the induced complex. Rather than simply blocking androgen signaling, it uses AR as a tumor-associated handle to disrupt a different cellular dependency. The trial explores whether this approach can provide another oral option after androgen-directed treatment, where taxanes, biomarker-selected PARP inhibitors, and PSMA radioligand therapy are among established alternatives.