mCRPC in focus
Transcript: JNJ-6420 shows potential for mCRPC
Dr Alexander Chehrazi-Raffle
Interview recorded June 2024. All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
So JNJ-6420 is a Human Kallikrein 2 or hK2 targeted monoclonal antibody conjugated to Actinium-225. hK2 is encoded by KLK2 and is a high membranous expression in prostate cancer, much like HK3, which is more commonly referred to as PSA. So JNJ-6420 preferentially binds to the membrane associated form of hK2 and then delivers the payload of Actinium-225, which is an alpha emitting radioisotope. So in this first inhuman phase 1 study that was reported at ASCO, patients were required to progressed on at least one ARPI. Prior chemo was permitted. The primary endpoint was safety and identifying the recommended phase 2 dose. Dose escalation was first performed with a fixed dosing schedule of 50 to 300 microcuries, but was then amended to a adaptive strategy that went to a maximum of about 5-600 microcuries. At baseline, approximately 50% of patients have received two or more ARPIs and nearly two thirds have received prior chemotherapy.
So quite a heterogeneous group. Persistent grade 3/4 thrombocytopenia was observed in 13 patients, most of whom received a cumulative dose of greater than 500 microcuries, whereas it occurred only in 1 out of 26 patients with a cumulative dose of 250 to 400. Of note five patients suffered from interstitial lung disease including two deaths. So that's gonna be something that the investigators have to keep a close eye out for going forward. Among patients who received 250 microcuries PSA50 was 44%, and PSA90 was 9% with an overall response rate of 18%. Adaptive dosing in which patients receive multiple infusions greater than 12 weeks apart are currently underway, and that might mitigate the risk for some of the toxicities that were seen. So this study was important because it was the first report of therapy that binds to hK2, which may represent a novel target in mCRPC. Also, it's one of the first studies to come out and report outcomes from Actinium-225, which is a highly active alpha emitting radioligand that holds a great deal of promise in contrast to the beta emitting ligand such as lutetium.
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