UPDATE: JNJ-6143 RIPTAC Advances to Randomized Phase 3 Trial With Overall Survival Endpoint

A newly registered phase 3 clinical trial will evaluate JNJ-6143 (JNJ-101556143 or HLD-0915), the first oral RIPTAC therapy investigated in prostate cancer, following encouraging phase 1 results presented at ESMO 2026. The study represents an important step toward determining whether this experimental treatment can extend survival in patients with metastatic castration-resistant prostate cancer (mCRPC), also referred to as metastatic androgen pathway modulation-resistant prostate cancer (mAPMR).

JNJ-6143 uses an unusual mechanism that brings the androgen receptor (AR) into an abnormal complex with BRD4, a protein essential for cell survival. Rather than simply blocking androgen signaling, the drug exploits AR expression to disrupt critical cellular functions and trigger cancer cell death.

The randomized, double-blind, placebo-controlled phase 3 trial plans to enroll approximately 400 patients with progressive mCRPC who have already received the life-prolonging treatments for which they are eligible and have access. Participants will receive either oral JNJ-6143 once daily plus best supportive care or matching placebo plus best supportive care. Androgen deprivation therapy will continue in both groups.

Importantly, overall survival is the primary endpoint, with secondary assessments including radiographic progression-free survival, pain progression, skeletal-related events, and safety. The study is expected to begin in November 2026, with primary completion currently estimated for February 2028.

The decision to advance JNJ-6143 into phase 3 follows promising phase 1 findings. At the selected 50 mg daily dose, confirmed PSA50 and PSA90 responses occurred in 77% and 48% of patients, respectively. Among 16 patients with measurable disease, 12 achieved confirmed radiographic responses, corresponding to an objective response rate of 75%. These findings were particularly encouraging given the heavily pretreated population.

Clinical trial.