UPDATE: JNJ-6143 Shows Early Activity in Advanced Prostate Cancer

Updated phase 1 results provide further evidence of activity for JNJ-6143, previously known as HLD-0915 and also referred to as JNJ-101556143, in heavily pretreated metastatic castration-resistant prostate cancer. Following our previous coverage of its initial results and a separate phase 2 trial, the new findings add dose-specific outcomes and exploratory molecular data.

JNJ-6143 is an oral RIPTAC that brings the androgen receptor and BRD4 into an abnormal complex, disrupting BRD4 function and triggering cancer cell death. It uses AR as an anchor rather than simply blocking androgen signalling.

The study treated 52 patients, who had received a median of six previous therapies. Among the 17 patients receiving 50 mg daily, confirmed PSA reductions of at least 50% and 90% occurred in 71% and 41%, respectively. Five of seven patients with measurable disease achieved partial responses, four of which were confirmed. Median follow-up was 7.1 months, with 14 patients continuing treatment.

Of particular interest, four of five patients with PTEN mutations or deletions achieved a PSA50 response. Responses were also observed in patients with alterations involving TP53 or RB1, AR amplification, AR ligand-binding-domain mutations, and AR-V7 expression. These findings suggest that activity can occur despite several molecular features associated with treatment resistance. However, the subgroups are very small and may overlap: they do not establish PTEN loss, or any other alteration, as a predictor of benefit.

Across all doses, 10% of patients experienced treatment-related adverse events of grade 3 or higher. At 50 mg, common treatment-related events were mild or moderate; one patient experienced grade 3 or higher anemia. No dose reductions or discontinuations due to adverse events were reported in this cohort. The findings support 50 mg daily as the preliminary optimal dose for further development.

Source.

Clinical trial.