ESMO26: Halda buy delivers a win for J&J in prostate cancer
A drug at the heart of Johnson & Johnson's $3 billion takeover of Halda last year, JNJ-6143, has shown promise in an early-stage trial in heavily pretreated prostate cancer.
JNJ-6143 (formerly known as HLD-0915) is the lead candidate emerging from Halda's RIPTAC (Regulated Induced Proximity Targeting Chimaera) platform, which generates bifunctional, oral drug candidates designed to simultaneously bind to a tumour-specific protein on one end and to an effector protein on the other.
The first-in-class drug binds to both androgen receptors and BRD4, a protein crucial for cell survival, bridging them to form an abnormal complex that disrupts BRD4 function and triggers programmed cell death (apoptosis).
In the phase 1/2 trial reported at ESMO, 77% of 31 evaluable patients with metastatic castration-resistant prostate cancer (mCRPC) who received a 50 mg dose of JNJ-6143 saw their levels of PSA, a blood marker used to monitor prostate cancer, fall by at least 50%. Furthermore, PSA levels fell by at least 90% in 48% of patients.
An analysis of patients whose tumours could be measured using imaging found that 69% of them had a confirmed complete or partial response. Lead investigator Benjamin Garmezy of the Sarah Cannon Research Institute in the US told delegates at ESMO that the findings suggest JNJ-6143 is "highly active" in this mCRPC population, despite receiving a median of six previous therapies.
The 50 mg dose also had an encouraging safety profile, with less than 60% of patients experiencing any form of treatment-related adverse event, with only 10% of them experiencing a serious (Grade 3 or higher) TRAE and only one subject discontinuing treatment. The most common side effects were nausea, elevated cholesterol levels, and elevated triglyceride levels.
"These early data suggest that JNJ-6143 has the potential to combine high tumour selectivity and robust efficacy with a favourable safety profile and convenient oral administration," said Garmezy.
J&J has now started an open-label, single-arm phase 2 trial of the RIPTAC drug, at a 50 mg dose delivered in 28-day treatment cycles until confirmed radiographic progression, that will enrol around 100 patients with metastatic CRPC.
The results provide an endorsement of Halda's platform, which has also given J&J other candidates for breast, lung, and other cancers, as well as some with applications beyond oncology.
