Let me try to answer (happy to be corrected)
- "Why would J&J be presenting/Why was it accepted by ASCO?"
- ASCO (or any legitimate conference or journal) acceptance is based on the quality of the work itself (importance to science being a major consideration). The results, whether positive, neutral, or negative, must not influence the decision to accept (if that happens, you create publication bias). JNJ will know too well not to engage in such.
- JNJ’s (Jansen’s) Clinical Data Transparency statement says: “We seek to publish, in peer-reviewed journals, results from all company-sponsored pharmaceutical Phase 2 through 4 clinical trials and Phase 1 trials in patients. Studies that terminate early (prior to pre-specified study end date) are included in our commitment to publish, provided they yield scientifically or medically important results”.
- "The patient who died had Covid which would likely be not treatment related?"
- From the limited info so far, they have classed it as a Treatment Emergent Adverse Event (TEAE), as it occurred once treatment had started. Further; not all Covid positive patients die from Covid, plus in the study almost all patients developed some adverse effects from treatment: 61% classified as Grade 3 or higher (Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event).
- "Despite the poor results their HREC is continuing the trials for patients who want to continue treatment despite knowing the interim results - should we interpret it as a serious lack of alternatives?"
- The continuation – I do not know! But the report mentions they are evaluating “adaptive dosing”. I do not know what this means with regards to continuation – are they analyzing what they have, or have they recruited more? The aim was to recruit about 50, and they managed to get 64, which suggests they are done.
- The timing between when the patients died and when HREC analysis would have allowed continuation is not in the reports so no idea what they decided post the 4 deaths.
- Lack of alternatives: Probably not the case – Plutivo is available and per Report 2, it had better results in the Phase 3 trial.
ALSO WORTH NOTING (Asper Trial protocol)
Primary Outcomes
- Number of Participants with Adverse Events (AEs)
- Number of Participants with Dose-Limiting Toxicity
- Number of Participants with AEs by Severity - Grade 1 (Mild) to Grade 5 (Death)
Secondary Outcomes
- PSA response rate is defined as the percentage of participants with a decline of PSA of 50 percent (%) or more from baseline and that is subsequently confirmed.
- Plus Others
BIG QUESTION: Will JNJ continue?
The adverse effects were common and quite serious. 61% severeand 6% deaths. But we know that the objective was to determine the recommended dose, andindeed, a ‘cumulative dose cap’ and an ‘adaptive dosing schedule’ have beenrecommended by the researchers. Whether that’s acceptable and justifiescontinuing or not – no idea!
In my view (from limited data): the comment that suggests inferior efficacy versus the standard (Pluvicto) isimportant. Yes, it’s a Phase 1 for JNJ-6420 and the Pluvicto trial referred to was a Phase 3: BUT, butto have inferior efficacy when you are dosing in a way that allows you to push to the maxtolerable (to a point where serious AEs are experienced), suggests to me that continuing would be a futileexercise!
The presentation or poster will have more information than what the reporters got from the abstracts so I think we will know more soon. Clarity will be at the conference too!
(20min delay)