New Poster presented this morning. Doc's comments indicate they are particularly interested in the indication of immunological activity. The short version of this is that it is probably the chemo's used which trigger an immune response but Indoximod is inhibiting the checkpoints so the immune response is becoming apparent. This is exactly what we want to see happen! Standard of Care demonstrated a 23% response whereas this is seeing 42% rate. Encouraging indeed!
A, does every message board have it's own version of pharmajedi?
B. if A, are they all short?
C. is there a psychological explanation that they share the same characteristics? ie self appointed pontiff of trading, all seeing eye, savior of the financial world, knows FAR more than anybody else could ever hope to know?
1. ALL of the living patients are censored. When the trial gets to the endpoint, (442-444 events?) There will be 276-278 patients still alive. Those will all be considered censored and recorded on the Kaplan Meier plots as a tick mark, not a step down. BUT... they are all also past 30 months.
2. There may be some who are lost to follow up. Those are also indicated as a tick mark. These patients may just have decided they are tired of treatment and decide not to go back - spend their life on the golf course, whatever... it happens. Others move away from their treatment center and basically drop out of the trial. They might continue treatment at another hospital out of trial. Many circumstances. They may die, but not be recorded as such. These show up on the plot as a tick mark without a drop down.
At the interims, the company DID use a consultant to find/round up as many of the patients as possible. But this time, they would not need to do that. Censoring becomes less an issue as the trial moves forward.
Some info, some thoughts related to your question...
At 442 events, the trial is un-blinded and the data is compiled, examined, and evaluated statistically. At 442nd event, you will have 280 patients still alive. (722 - 442 death events) Those patients alive would plot onto the Kaplan Meier as "right censored" at their last known contact point. There might also be some others who have lost contact (moved, quit, or unknown status) who would also show up on the plot at last known date.
There is no value or reason to wait further because the trial design is based on the 442 events. And November does not remove a patient from censorship. Death does. Incidentally, all living patients are now in the trial for more than 28 months since surgery - growing month by month so by May, this number will be over 31 months.
It is also important to note that the SPA for the trial specifies statistical significance based on Log Rank test. However, that mostly applied to the interim analysis points. When the trial reaches full 442 events, the company may choose additional statistical methods. They can take and present any evidence of success to the FDA.
No, they are different pathways, but do similar things. Here is my understanding, but I'm just an architect, not a biologist.
Tumors use PD-L1 and PD-L2 ligands to engage the PD-1 receptor on a t-cell to make it deactivate. Keytruda is an antibody that grabs the PD-1 receptor and blocks this interaction from happening. This keeps the t-cell active to kill tumor.
IDO is another different pathway (also from tumor cell) that directly activates the T-regulatory cells which, in turn, tell the T-cell to shut down. IDO inhibitors keep IDO from communicating with T-regs which keep the t-cells active
In theory, these two should be able to work TOGETHER and get a better response.