Oncology News Central (ONC)ASCO24: J&J Reports Four Patient Deaths in Early-Stage Prostate Cancer Trial

Phase I Study Reveals J&J’s JNJ-6420 Shows Potential in Prostate Cancer with Notable Safety Concerns

Johnson & Johnson’s Phase I study of JNJ-6420, a targeted radiopharmaceutical for metastatic castration-resistant prostate cancer, reported four patient deaths, highlighting both its promising efficacy and significant safety concerns. Interim data, presented ahead of the American Society of Clinical Oncology annual meeting, shows a potential for substantial biochemical and radiographic responses but underscores the need for careful management of adverse events.

Key Points:

• Study Design and Participants:
  • Phase I study of JNJ-6420 in metastatic castration-resistant prostate cancer.
  • 57 patients received at least one dose; 31 patients stayed on treatment for 24 weeks or longer.
  • Three patients showed confirmed objective response; one achieved complete response.
• Efficacy Results:
  • Almost half of patients receiving at least a 150-μCi dose experienced a 50% decline in prostate-specific antigen levels.
  • 14% of patients reached the 50% PSA decline benchmark.
  • At six months, the disease control rate was 28.1%.
• Safety and Adverse Events:
  • More than 60% of patients experienced treatment-emergent adverse events (TEAE) of at least grade 3 severity.
  • Approximately 37% of patients had serious TEAEs.
  • Common adverse events included anemia, low platelet count, and abnormal reductions in white blood cells.
  • Nine patients discontinued the study due to severe side effects related to the study drug.
• Mechanism of Action:
  • JNJ-6420 uses an anti-hK2 antibody to deliver an actinium-based radioligand.
  • The radioligand emits high-energy alpha particles, targeting prostate cancer cells specifically.
• Industry Context:
  • J&J joins other companies investing in targeted radiopharmaceuticals.
  • Bristol Myers Squibb acquired RayzeBio for $3.6 billion; its lead program RYZ101 targets gastroenteropancreatic neuroendocrine tumors and small-cell lung cancer.
  • AstraZeneca acquired Fusion Pharmaceuticals for up to $2.4 billion; its lead program FPI-2265 will compete with JNJ-6420 in prostate cancer.
  • Novartis and Eli Lilly also invested significantly in the radiopharma field recently.

Actinium-225, used in JNJ-6420, has a half-life of about 10 days, which allows it to deliver potent radiation to cancer cells over a short period while minimizing long-term radiation exposure.

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