Replies to post #153800 on Biotech Values

[jq1234]

In the IC arm, the median OS of the 5 HG non TN patients was ~11.3 months vs 5.5 months for the 6 HG TN patients. I find It hard to believe in the 5th or 6th line setting the type of chemo or TN status still makes such a big difference. Patients at this stage would be too refractory regardless of TN status. I am not sure whether it's correct to characterize chemo given to non-TN as active vs that to TN as placebo.

Those 5 HG non TN you picked had the best OS among ALL IC patients in the trial. Obviously you can look at this two different ways:

1. High G and TN IC arm represented underperformers in the trial, thus exeggerate 011 OS survival in this group - graph 4.

2. Even with super performers on HG IC arm like that with small smaple size, there is still strong OS trend for 011 over IC for high G group. Thus, it highlights G status as predictor of outcome - graph 3.

To look at 1 further, if you look at TN regardless of G status for IC arm (graph 2) - it is reasonable to look at this under the assumption that IC arm results don't change much due to G status - mOS=6.5, it is still underpormed the overall IC arm mOS=7.4. It is consistent with the assumption that TN status is negative indicator of outcome in IC arm. So even if in larger sample, high G and TN IC arm perform better than IC arm in graph 4, it doesn't contradict/invalidate the overall result in graph 3 and 4. To me, the question is how large a sample size is needed to confirm the benefit.

[jq1234]

Finally the way the crossover patients were analyzed in both control and cdx011 is a head scratcher. There is the inherent bias only patients who is fit or disease stable get the chance to cross over. The company must have felt it compelling to include such patients in both treatment arm as otherwise the PFS difference would be less pronounced. The correct way would be to censor on last SD visit before crossover and include in only the control arm.

I'd agree on PFS analysis alone. I think they did this due to really small sample size for high G and TN patients mainly due to low entry criteria (5% GPNMB). However, OS analysis is done traditionally which is great. Thus the 3 super OS responders (OS 11.3m, 12.3m, 21m) in high G and non TN IC arm (5 of them with 11.3m mOS you mentioned in your post) could be due to crossover to 011, which would make 011 current OS trend more impressive.

From poster:

Patients who initially received Investigator’s Choice and subsequently crossed over to receive CDX-011 (n=15) are included in the PFS analysis for each treatment . These patients, with a median OS of 12.5 months, are assigned to the Investigator’s Choice arm only for OS analysis. Median OS for the remaining IC patients who did not cross over is 5.4 months.

[exwannabe]

Finally the way the crossover patients were analyzed in both control and cdx011 is a head scratcher. There is the inherent bias only patients who is fit or disease stable get the chance to cross over. The company must have felt it compelling to include such patients in both treatment arm as otherwise the PFS difference would be less pronounced. The correct way would be to censor on last SD visit before crossover and include in only the control arm.

Disagree.

The crossover was after progression. So on the IC arm the PFS data is complete prior to progression. Saying they should censor at that point makes no sense.

As they crossover, they are just like any other patient enterring the trial. Start a new clock at crossover time, and the PFS from there is just another data point.

As to "The company must have felt it compelling to include ...", that is a fairly extreme statement. Why do you not consider it reasonable that this was the SAP?