ESMO Congress 2026

The androgen receptor (AR) remains a central therapeutic target in metastatic castration-resistant prostate cancer (mCRPC), but the field is clearly evolving beyond conventional AR pathway inhibitors (ARPIs); AR amplifications, mutations, splice variants, and rearrangements are highly enriched in mCRPC and often portend worse prognosis.

The ESMO 2026 presentation reported the Phase 1 trial of JNJ-6143 (n=105) establishing a recommended Phase 2 dose (RP2D) of 50 mg orally; at this dose, any-grade treatment-related adverse events (TRAEs) occurred in <60% of patients, PSA50 response rate was 77%, PSA90 was 48%, confirmed objective response rate (ORR) was 69%, high PSA response rates were observed irrespective of high-risk molecular features, and median duration of response was 11 months.

Post-meeting media coverage added: BioSpace noted an ORR of 75% (12 of 16 patients with radiographically measurable disease); Chinese industry outlets confirmed the 75% ORR and disclosed Johnson & Johnson's $3.05 billion acquisition of Halda Therapeutics, with JNJ-6143 (formerly HLD-0915) being the first RIPTAC-platform molecule to enter clinical testing.

These results mark the first-in-class oral AR-targeted RIPTAC — degrading AR via BRD4 recruitment — demonstrating clinical activity in heavily pretreated mCRPC including high-risk molecular subtypes; limitations include the early Phase 1 stage, small measurable-disease cohort for ORR assessment, and the need for Phase 2 data to define long-term safety and resistance mechanisms.