Thought on the various cancers in the basketOne of the questions raised here after 1a discussion was why did we only hear about Prostate (a cancer with mid levels of Sort1 staining but perhaps still enough to make a difference) and endometrial (one that's high sort1)? Why didn't we hear more about ovarian, melanoma or TNBC since those are at the higher level?
We know one answer is that the nature of the 1a was that it was always going to be a small sample size (18 or so enrollees). The size and randomness didn't work toward an even split of all types.
I also wonder if there's another reason, and it could be contributing to why 1b could be moving a bit slower with enrollees. In looking at the typical sequence of therapies as TNBC or HER+ types move through their progression in stages and addressable therapies, we can see that there are now more and more helpful therapies and combo therapies for stage 4 and metastatic recurring stages. In looking at the recommended progressions, the general strategy according to cancer orgs is (excluding surgery and radiation) to start with docetaxol and Xeloda usually, then a PARP inhibitor (Lynparza).
If you hit Stage 4 you might move on to rubicin types, other taxols, then on to platinums and various combos. This stage also introduces immunotherapy drugs (the PD-L1 targeted ones like Keytruda). Then you move to the ADC Trodelvy if two others have failed and you become recurrent. You may move to Enhertu too if conditions warant. For the HR+ ones you can add in CDK inhibitors and other kinase inhibitors. For the HER2 low cancers you would move on to Enhertu. We know that's become the market share leader with a few cancer types now.
After that, the current last line treatments are a large list of various combo's with some of the above and specific types of drugs depending on where the metastatic spread is. Some are just to alleve pain and aren't as much about therapy at this point. TH-1902 would be targeting usage at this point --when all else has failed --at the outset to get approval and breakthrough.
But you can see the issue with getting a lot of TNBC or HE+ enrollees. They currently have a lot of options to use first and they've been fairly effective options (keytruda, enhertu, trodelvy). There's also a lot of combo trials with various known drugs and I can see many of those being the first things doctors might recommend for the last stage -- they have seen strong responses and perhaps combining it may extend life 6 months or so, so why not? I'm purely putting this out there as a possible reason why it's likely a lot harder getting "3-month" phase 1b enrollees in TNBC and some of these other larger cancer's in the basket. Those patients get existing proven effective treatments for longer, and combos are an attracive clinical trial. Then they are too advanced to enroll in TH1902 or any others. They give the powerful approved drugs another shot in combo with something else.
The only counter-veiling argument would be that these are very large patient markets so maybe there's not an issue finding 10 or 25 patients given the large overall base hitting the Stage 4 and Stage 4+ metastices for some of these. I would agree with that. But it's also probably why you do really need a proactive recruiter in your investigative group at each hospital. Given all the trials MD Anderson and Cedars Sinai are doing, it's no surprise we haven't heard anything from either (they haven't been mentioned in any PR, but would certainly be communicating with Marsolais and it could eassily be wrong). The MD Anderson lead just gave a talk about a new therapy at a conference and it was an immunotherapy drug. As I said before, I don't even see the two Dr & DrMrs Mita at Cedars Sinai even listing the trial as open. It may just be the only places with real advocates are the PA clinic, the two in Detroit and maybe the Dallas specialty one. This could be why it's all a bit slower than we hoped for.
Questions worth asking them about if anyone calls in to IR or Mgmt for an update!