Ann: LuPIN Survival Outcome Confirmed by Conference Presentation, page-17

OK so i wanted to compare the LuPIN trial to the results from the TheraP trial that was posted to this thread earlier. Feel free to comment on my assessment and highlight areas where you think I may be wrong.

https://meetinglibrary.asco.org/record/195203/abstract

Background

TheraP is investigating LuPSMA as a stage 3 treatment for prostate cancer by comparing it against cabazitaxel.

The LuPIN trial is combining Veyonda with LuPSMA as a stage 4 treatment option for Men who have exhausted all other prostate cancer treatment options.

Results

1) Progression Free Survival

TheraP Trial: At a median follow-up of 18.4 months, PFS was significantly longer in those assigned Lu-PSMA rather than cabazitaxel (rates at 1y 19% [95%CI 12-27%] vs 3% [1-9%], hazard ratio (HR) 0.63, 95%CI 0.46-0.86; p = 0.003; 173 events). Similar benefit was seen for rPFS (HR 0.64, 95%CI 0.46-0.88; p = 0.007; 160 events) and PSA-PFS (HR 0.60 95%CI 0.44-0.83; p = 0.002; 172 events). ORR in 78 men with measurable disease was significantly greater in the LuPSMA arm (49% vs 24%, RR 2.1, 95%CI 1.1-4.1; p = 0.019).

LuPIN Trial: Disease progresses at a much quicker rate when using Veyonda (the median PSA PFS using Veyonda was 7.5 months with a confidence interval of 5.9-9.0 months), which is likely confirmation that patients that are part of this trial are already in a very bad state.

2) Pain response

TheraP Trial: In 90 men with pain at baseline, pain responses occurred in 60% in the Lu-PSMA arm vs 43% for cabazitaxel (RR 1.42, 95%CI 0.84-4.48; p = 0.10).

LuPIN Trial: Unsure of the pain response for the LuPIN trial, but 2/4 patients in the 1200 mg cohort recorded a pain response (>30% reduction from baseline on the Brief Pain Inventory) in the DARRT-1 trial.

3) Safety

TheraP Trial: Patient-reported global health status was similar (LuPSMA 64 [95%CI 61-67] vs cabazitaxel 60 [57-64]) with significantly better outcomes reported for fatigue (34 [95%CI 31-37] vs 40 [36-43]), social functioning (79 [76-82] vs 73 [69-77]), insomnia (24 [20-27] vs 29 [25-33]) and diarrhoea (8.3 [5.6-11.0] vs 15.6 [12.6-18.6]) domains. No PRO domains were superior for cabazitaxel. G3-4 AEs were similar to previously reported (33% vs 53%).

LuPIN Trial: Veyonda appears safer with anaemia and fatigue the only Grade 3 toxicities, although it’s difficult to know whether to ascribe these Grade 3 toxicities to Veyonda or LuPSMA used in the study.

4) Overall Survival

TheraP Trial: OS data remains immature (90 deaths).

It’s challenging to compare overall survival between the TheraP and the LuPIN trial since we don’t yet know the median overall survival data for the TheraP study or overall survival for the LuPIN study. The TheraP study is currently sitting at a median follow-up of 18.4 months with 90 deaths out of 200 trial participants. So this would mean median survival for the LuPSMA group is probably much higher than the 13.5 months that is often referenced from a previous study. For the LuPIN study median OS was 19.7 months with a confidence interval of 9.5-30.0 months, and 34% (19/56) men remain alive.

My Overall Assessment

It’s difficult to say whether the increase in survival from the LuPIN study is due to Veyonda or LuPSMA, hence the need for a placebo-controlled clinical trial.

After comparing the TheraP trial results to the LuPIN trial results, LuPSMA is likely to offer a much greater survival benefit than the 13.5 median survival previously reported. I would estimate that the median survival for LuPSMA in the TheraP trial will probably be around 24 months, although that data has not been released yet. This is especially so when you consider the progression free survival (PFS) data which measures the time to disease progression.

The only positive for the LuPIN trial is that the median OS of 19.7 months was achieved in Men who had exhausted all prostate cancer treatment options. The obvious question is how much of the observed benefit was due to LuPSMA or Veyonda.

It currently appears less likely that Novartis will need Veyonda whether for FDA approval or to capture a more sizeable market, especially less so in the short term. It is also possible that Novartis won’t need Veyonda at all, but the only way we would know for sure is after a placebo-controlled clinical trial, including at an earlier stage – probably paid for by NOX – and thus it appears less likely there will be no commercial deals forthcoming for NOX in 2021.

Disclaimer: I used to own NOX, but sold out last week. I still like NOX and will be watching closely.

Not advice, DYOR, GLTAH