RE:RE:RE:RE:RE:RE:RE:RE:Fireside Chat on August 10 There already existed validated her2 assays, they've been used in the clinic for a very long time for trastuzumab treatment. It would be foolish not to use it. But even then when trialing TE they still took a greater range of her2 levels than are used for trastuzumab because maximizing the treatment population is an important outcome. They could have just looked to treat her2 high patients and maximize ORR, they didn't. They treated her2 low expressors and now the drug doesn't just look great, it looks groundbreaking. You discover these things not by theorizing but by testing.
The way to look at this is at the end of an expanded 1b (25 patients if they go that route) we will have a ball park figure for the ORR in an unscreened population. If the % is high enough then they've struck gold, if the % is low then they have the potential to improve that with screening. If they have the Sortilin expression levels of their patients by then and the patterns fit they may be able to put a convincing argument together for an ORR in a screened population. They are aiming for a full, unscreened population, that's gold. If they miss that they can still win with a screened population. To justify to the fda that your population is the whole late-stage population of a particular cancer type you have to gather data for that population, so you take all-comers. I'm sure if that doesn't work out they'll rapidly pivot. Even if they have to pivot the data they collect from the all-comers is going to inform exactly how that pivot occurs.
There is no data at the moment to say what is the optimum path forward,they will generate that data with an all-comer strategy. It might seem like they are sacrificing a possibly better ORR but in reality they are learning what this drug is capable of. You can only do that by generating data.
LouisW wrote: Agreed. Running the trial without SORT1 expression is also my consern. Immunomedics didnt evaluate the trop2 expression prior to the treatment since they claimed that 88% of the patients expressing Trop2 based on the TMA data. However, Her2 expreesion level was confirmed prior to treatment of Trastuzumab Emtansine. Maybe TH will do IHC staining prior to treatment in the larger trial. They cannot let the probability determine the fate of the trial.