Garmezy Discusses Unanswered Questions for JNJ-6143 in Prostate Cancer

JNJ-6143 has shown antitumor activity in heavily pretreated advanced prostate cancer, but questions remain about how resistance develops and whether the therapy can provide durable benefit earlier in the disease course, according to Benjamin Garmezy, MD, associate director of Genitourinary Cancer Research at Sarah Cannon Research Institute, in an interview with Targeted Onc^TM.

JNJ-6143 is an investigational oral regulated induced proximity targeting chimera (RIPTAC) designed to bring together 2 proteins: bromodomain-containing protein 4, which supports cell survival, and the androgen receptor (AR), which is highly expressed in prostate cancer cells. This interaction is intended to disrupt cancer cell function and induce cell death. The agent is being evaluated in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed after at least 1 AR pathway inhibitor.¹

In the phase 1 study (NCT06800313), patients had received extensive prior treatment, with a median of 4 previous therapies. Among patients with measurable disease treated with 50 mg once daily, a subsequent Johnson & Johnson update reported a confirmed objective response rate of 75% (n = 12/16). In the same dose cohort, 77% of 38 patients had a confirmed prostate-specific antigen decline of at least 50%, and 48% had a decline of at least 90%. At the data cutoff, 71% of patients receiving 50 mg once daily remained on treatment.

Garmezy identified resistance as a key scientific question. Although some patients experienced tumor responses, others eventually had disease progression. Among patients with measurable disease, the median duration of response was 11 months, as discussed in the interview. The reasons some tumors stop responding are not yet understood, and Garmezy said additional tissue samples will be important to investigate those mechanisms.

Biopsies collected at progression could help researchers identify molecular changes associated with resistance and determine whether tumor features are linked to response duration. Garmezy said he hopes the phase 2 development program will help address this question by enabling investigators to collect additional samples. The phase 2 study (NCT07832292) is part of JNJ-6143's ongoing clinical development.

A second unanswered question is how early in the treatment course JNJ-6143 could be used. The phase 1 data come from a heavily pretreated population, and additional research is needed to establish whether activity in that setting will translate to patients treated earlier. Garmezy said a randomized phase 3 study in the refractory population would be an important next step. If results support further development, investigators could explore the therapy in first-line mCRPC and hormone-sensitive prostate cancer.

Early-phase trials are also evaluating JNJ-6143 in first-line settings, including combinations with androgen deprivation therapy and approaches intended to spare patients from this treatment, Garmezy said. Its efficacy and long-term durability in these earlier settings remain unknown.

These questions will shape the next stages of JNJ-6143 research: determining why resistance occurs, identifying which patients may benefit, and establishing whether the investigational therapy can maintain its activity when introduced earlier in prostate cancer treatment.

REFERENCE

1. Johnson & Johnson reports 75% tumor response rate in advanced prostate cancer with JNJ-6143, a first-in-class RIPTAC molecule. News release. Johnson & Johnson. October 25, 2026. Accessed November 10, 2026. https://tinyurl.com/3m9h5wka