Actinium-225 alpha therapyfrom J&J? (what we know so far - per...

Actinium-225 alpha therapyfrom J&J? (what we know so far - per info gleaned from an abstract due to be reported next week)


SOME BACKGROUND

Clinical Trial Title: A Phase 1 Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer

Link for full details: https://clinicaltrials.gov/study/NCT04644770

[Note: JNJ-69086420 (also referred to as JNJ-6420) is an alpha-particle emitter (as opposed to Cu67 which is a beta emitter)]

Study Objectives

1. To determine the recommended Phase 2 dose(s) (RP2D) of JNJ-69086420 in Part 1 (Dose Escalation), and,
2. To determine safety and preliminary signs of clinical activity at the RP2D(s) in Part 2 (Dose Expansion)

Other Trial Details

• An open-label clinical trial

• Targetting men 'aged ≥18 years with advanced metastatic castration-resistant prostate cancer who have previously received at least one prior androgen receptor pathway inhibitor'.

THE REPORTS - (so far)

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REPORT 1: ASCO: J&J's radioligand spurs responses, but 4 deaths mar early results

Link to this report: https://www.fiercebiotech.com/biotech/asco-jjs-radioligand-spurs-responses-4-deaths-mar-early-result

Findings (summary) - almost verbatim

• 64 patients received at least one dose of JNJ-6420, with safety data being recorded for 57 who had received 150 μCi.
• 35(61%) experienced grade 3 or higher treatment-emergent adverse events (TEAEs), and 21(37%) had a serious TEAE. Almost all patients experienced some sort of TEAE.
• Four patient deaths occurred, linked to repeated dosing of JNJ-6420. Two deaths were associated with interstitial lung disease (ILD), one with COVID-19-related respiratory failure, and one with decreased appetite/hypotension.
• ILD occurred in patients receiving cumulative doses of 750 μCi or higher.
• Thrombocytopenia (low platelet count) was reported in 63% of treatment-emergent adverse events (TEAEs), and ILD in 9%.
• Common TEAEs included anemia, lymphopenia, and leukopenia.
• Nine patients discontinued treatment.
• JNJ-6420 demonstrated a reported PSA50 rate of 45.6%, indicating a positive prostate-specific antigen response associated with prolonged survival.
• The drug produced one complete response, two partial responses, and three confirmed objective responses.
• Notable clinical, biochemical, and radiographic responses were observed in patients receiving doses of 150 μCi and higher, with durable responses noted up to 112 weeks.

TO MITIGATE RISK: the study recommends a "cumulative dose cap and adaptive dosing schedule'. Evaluation of adaptive dosing is ongoing.

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REPORT 2: Ahead of ASCO, J&J reports mixed data on next-generation radiopharmaceutical

Link to this report: https://www.statnews.com/2024/05/23/johnson-and-johnson-radiopharmaceuticals-prostate-cancer/

Highlights:

• "... An early-stage clinical trial of a radiopharmaceutical drug developed by Johnson & Johnson showed some signs of efficacy in prostate cancer patients, newly released data show, but four participants in the trial died.
• "... 18% of participants on a mid-level dose of JnJ’s treatment had a complete or partial response. For comparison, approx. 29.8% of subjects in a Phase 3 trial of Pluvicto responded to the treatment..."

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I hope I have accurately represented the information that I found - and I hope this is useful to the Cu6 community.